11-18269312-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199161.5(SAA1):c.209C>T(p.Ala70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 148,460 control chromosomes in the GnomAD database, including 18,724 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 18724 hom., cov: 28)

Exomes 𝑓: 0.55 ( 148135 hom. )

Failed GnomAD Quality Control

Consequence

SAA1
NM_199161.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: -0.932

Publications

36 publications found

Variant links:

Genes affected

SAA1 (HGNC:10513): (serum amyloid A1) This gene encodes a member of the serum amyloid A family of apolipoproteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a major acute phase protein that is highly expressed in response to inflammation and tissue injury. This protein also plays an important role in HDL metabolism and cholesterol homeostasis. High levels of this protein are associated with chronic inflammatory diseases including atherosclerosis, rheumatoid arthritis, Alzheimer's disease and Crohn's disease. This protein may also be a potential biomarker for certain tumors. Finally, antimicrobial activity against S. aureus and E. coli resides in the N-terminal portion of the mature protein. Alternate splicing results in multiple transcript variants that encode the same protein. A pseudogene of this gene is found on chromosome 11. [provided by RefSeq, Jul 2020]

SAA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011088252).

BP6

Variant 11-18269312-C-T is Benign according to our data. Variant chr11-18269312-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 18108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA1	NM_199161.5 link	c.209C>T	p.Ala70Val	missense_variant	Exon 3 of 4	ENST00000356524.9	NP_954630.2	P0DJI8
SAA1	NM_000331.6 link	c.209C>T	p.Ala70Val	missense_variant	Exon 3 of 4		NP_000322.3	P0DJI8
SAA1	NM_001178006.3 link	c.209C>T	p.Ala70Val	missense_variant	Exon 4 of 5		NP_001171477.2	P0DJI8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAA1	ENST00000356524.9 link	c.209C>T	p.Ala70Val	missense_variant	Exon 3 of 4	1	NM_199161.5	ENSP00000348918.4		P0DJI8

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

81134

AN:

148342

Hom.:

18715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.532

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.593

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.597

Gnomad OTH

AF:

0.510

GnomAD2 exomes

AF:

0.479

AC:

73276

AN:

152964

AF XY:

0.479

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.552

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.552

AC:

741180

AN:

1343586

Hom.:

148135

Cov.:

AF XY:

0.547

AC XY:

360796

AN XY:

659288

show subpopulations

African (AFR)

AF:

0.501

AC:

14629

AN:

29218

American (AMR)

AF:

0.445

AC:

12585

AN:

28292

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

8199

AN:

21404

East Asian (EAS)

AF:

0.266

AC:

9950

AN:

37428

South Asian (SAS)

AF:

0.432

AC:

30695

AN:

71050

European-Finnish (FIN)

AF:

0.584

AC:

28553

AN:

48930

Middle Eastern (MID)

AF:

0.348

AC:

1853

AN:

5320

European-Non Finnish (NFE)

AF:

0.579

AC:

605706

AN:

1046342

Other (OTH)

AF:

0.522

AC:

29010

AN:

55602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

12038

24075

36113

48150

60188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19202

38404

57606

76808

96010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.547

AC:

81183

AN:

148460

Hom.:

18724

Cov.:

AF XY:

0.540

AC XY:

39240

AN XY:

72622

show subpopulations

African (AFR)

AF:

0.532

AC:

21639

AN:

40682

American (AMR)

AF:

0.502

AC:

7504

AN:

14946

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

1392

AN:

3410

East Asian (EAS)

AF:

0.277

AC:

1414

AN:

5110

South Asian (SAS)

AF:

0.453

AC:

2143

AN:

4734

European-Finnish (FIN)

AF:

0.593

AC:

6166

AN:

10400

Middle Eastern (MID)

AF:

0.361

AC:

104

AN:

288

European-Non Finnish (NFE)

AF:

0.597

AC:

39372

AN:

65936

Other (OTH)

AF:

0.505

AC:

1041

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.562

Heterozygous variant carriers

1543

3087

4630

6174

7717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.535

Hom.:

3270

ExAC

AF:

0.487

AC:

57822

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 30, 2018

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 30, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23437051) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

SERUM AMYLOID A VARIANT

Pathogenic:1

Jun 01, 1995

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

SAA1-related disorder

Benign:1

Apr 17, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.29

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.011

T;T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.35

.;.;T;T

MetaRNN

Benign

0.0011

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.93

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N;.;N

REVEL

Benign

0.011

Sift

Benign

0.74

T;T;.;T

Sift4G

Benign

1.0

T;T;.;T

Vest4

0.013

MPC

1.7

ClinPred

0.0042

GERP RS

-0.058

gMVP

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over