dbSNP rs11024595: SAA1:c.-50C>T (chr11-18266251-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_199161.5(SAA1):c.-50C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 153,192 control chromosomes in the GnomAD database, including 640 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.063 ( 638 hom., cov: 29)

Exomes 𝑓: 0.045 ( 2 hom. )

Consequence

SAA1
NM_199161.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Publications

11 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:

RNA5SP334 (HGNC:43234): (RNA, 5S ribosomal pseudogene 334)

RNA5SP334 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SAA1	NM_199161.5 link	c.-50C>T	upstream_gene_variant	ENST00000356524.9	NP_954630.2
SAA1	NM_000331.6 link	c.-197C>T	upstream_gene_variant		NP_000322.3
SAA1	NM_001178006.3 link	c.-111C>T	upstream_gene_variant		NP_001171477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAA1	ENST00000356524.9 link	c.-50C>T		upstream_gene_variant		1	NM_199161.5	ENSP00000348918.4

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9628

AN:

152168

Hom.:

636

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0282

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0627

Gnomad ASJ

AF:

0.0763

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0466

Gnomad OTH

AF:

0.0555

GnomAD4 exome

AF:

0.0453

AC:

AN:

906

Hom.:

Cov.:

AF XY:

0.0444

AC XY:

AN XY:

450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0781

AC:

AN:

128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.0750

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0359

AC:

AN:

696

Other (OTH)

AF:

0.0625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0634

AC:

9651

AN:

152286

Hom.:

638

Cov.:

AF XY:

0.0697

AC XY:

5193

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0285

AC:

1184

AN:

41562

American (AMR)

AF:

0.0627

AC:

960

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0763

AC:

265

AN:

3472

East Asian (EAS)

AF:

0.384

AC:

1990

AN:

5180

South Asian (SAS)

AF:

0.132

AC:

635

AN:

4824

European-Finnish (FIN)

AF:

0.121

AC:

1284

AN:

10602

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0466

AC:

3170

AN:

68022

Other (OTH)

AF:

0.0601

AC:

127

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

411

822

1233

1644

2055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0446

Hom.:

Bravo

AF:

0.0616

Asia WGS

AF:

0.265

AC:

918

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.72

(source)

DANN

Benign

0.63

PhyloP100

-1.2

PromoterAI

-0.055

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

Other links and lift over