rs1136747

Variant names:

Variant summary

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

The NM_000331.6(SAA1):c.224T>C(p.Val75Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 147,752 control chromosomes in the GnomAD database, including 23,233 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 23233 hom., cov: 28)

Exomes 𝑓: 0.60 ( 180767 hom. )

Failed GnomAD Quality Control

Consequence

SAA1
NM_000331.6 missense

Scores

Splicing: ADA: 0.00008927

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.68

Publications

32 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=0.0050112307).

BP6

Variant 11-18269327-T-C is Benign according to our data. Variant chr11-18269327-T-C is described in ClinVar as Benign. ClinVar VariationId is 1258441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000331.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SAA1	NM_199161.5	MANE Select	c.224T>C	p.Val75Ala	missense	Exon 3 of 4	NP_954630.2
SAA1	NM_000331.6		c.224T>C	p.Val75Ala	missense	Exon 3 of 4	NP_000322.3
SAA1	NM_001178006.3		c.224T>C	p.Val75Ala	missense	Exon 4 of 5	NP_001171477.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SAA1	ENST00000356524.9	TSL:1 MANE Select	c.224T>C	p.Val75Ala	missense	Exon 3 of 4	ENSP00000348918.4
SAA1	ENST00000532858.5	TSL:1	c.224T>C	p.Val75Ala	missense	Exon 4 of 5	ENSP00000436866.1
SAA1	ENST00000405158.2	TSL:5	c.224T>C	p.Val75Ala	missense	Exon 3 of 4	ENSP00000384906.2

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

88766

AN:

147632

Hom.:

23206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.568

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.576

Gnomad FIN

AF:

0.703

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.557

GnomAD2 exomes

AF:

0.534

AC:

63227

AN:

118470

AF XY:

0.532

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.486

Gnomad FIN exome

AF:

0.611

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.530

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.601

AC:

781752

AN:

1300906

Hom.:

180767

Cov.:

AF XY:

0.598

AC XY:

379637

AN XY:

635044

show subpopulations

African (AFR)

AF:

0.535

AC:

15086

AN:

28200

American (AMR)

AF:

0.500

AC:

11912

AN:

23808

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

8409

AN:

19654

East Asian (EAS)

AF:

0.533

AC:

18754

AN:

35186

South Asian (SAS)

AF:

0.532

AC:

35159

AN:

66062

European-Finnish (FIN)

AF:

0.682

AC:

32200

AN:

47244

Middle Eastern (MID)

AF:

0.372

AC:

1896

AN:

5096

European-Non Finnish (NFE)

AF:

0.614

AC:

627315

AN:

1021828

Other (OTH)

AF:

0.576

AC:

31021

AN:

53828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

Heterozygous variant carriers

9617

19234

28850

38467

48084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19432

38864

58296

77728

97160

<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:

0.601

AC:

88846

AN:

147752

Hom.:

23233

Cov.:

AF XY:

0.601

AC XY:

43410

AN XY:

72224

show subpopulations

African (AFR)

AF:

0.568

AC:

23038

AN:

40576

American (AMR)

AF:

0.542

AC:

8045

AN:

14852

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1565

AN:

3394

East Asian (EAS)

AF:

0.557

AC:

2767

AN:

4972

South Asian (SAS)

AF:

0.576

AC:

2721

AN:

4722

European-Finnish (FIN)

AF:

0.703

AC:

7284

AN:

10358

Middle Eastern (MID)

AF:

0.391

AC:

111

AN:

284

European-Non Finnish (NFE)

AF:

0.636

AC:

41750

AN:

65652

Other (OTH)

AF:

0.557

AC:

1143

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.574

Heterozygous variant carriers

1486

2972

4457

5943

7429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.634

Hom.:

3289

ExAC

AF:

0.551

AC:

63027

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.079

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.89

PhyloP100

1.7

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.17

Sift

Benign

0.034

Sift4G

Uncertain

0.019

Vest4

0.077

MPC

2.5

ClinPred

0.060

GERP RS

-3.1

gMVP

0.66

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000089

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over