Variant 11-18269774-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_199161.5(SAA1):c.288T>C(p.Ala96=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,613,852 control chromosomes in the GnomAD database, including 195,674 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 0.37 ( 12485 hom., cov: 32)

Exomes 𝑓: 0.49 ( 183189 hom. )

Consequence

SAA1
NM_199161.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=-1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SAA1	NM_199161.5 linkuse as main transcript	c.288T>C	p.Ala96=	synonymous_variant	4/4	ENST00000356524.9
SAA1	NM_000331.6 linkuse as main transcript	c.288T>C	p.Ala96=	synonymous_variant	4/4
SAA1	NM_001178006.3 linkuse as main transcript	c.288T>C	p.Ala96=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAA1	ENST00000356524.9 linkuse as main transcript	c.288T>C	p.Ala96=	synonymous_variant	4/4	1	NM_199161.5	P1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55743

AN:

152040

Hom.:

12486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.417

AC:

104900

AN:

251420

Hom.:

23428

AF XY:

0.420

AC XY:

57106

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0975

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.301

Gnomad SAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.491

AC:

717446

AN:

1461692

Hom.:

183189

Cov.:

AF XY:

0.486

AC XY:

353386

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0849

Gnomad4 AMR exome

AF:

0.433

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.309

Gnomad4 SAS exome

AF:

0.369

Gnomad4 FIN exome

AF:

0.451

Gnomad4 NFE exome

AF:

0.531

Gnomad4 OTH exome

AF:

0.449

GnomAD4 genome

AF:

0.366

AC:

55749

AN:

152160

Hom.:

12485

Cov.:

AF XY:

0.364

AC XY:

27056

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.435

Gnomad4 ASJ

AF:

0.325

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.504

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.428

Hom.:

6681

Bravo

AF:

0.355

Asia WGS

AF:

0.331

AC:

1151

AN:

3478

EpiCase

AF:

0.477

EpiControl

AF:

0.470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.34

DANN

Benign

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over