Variant chr11-18269319-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_199161.5(SAA1):c.216T>C(p.Ala72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 119,316 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 189 hom., cov: 29)

Exomes 𝑓: 0.16 ( 204 hom. )

Failed GnomAD Quality Control

Consequence

SAA1
NM_199161.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.185

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 -21 ACMG points.

BP4

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

BP6

Variant 11-18269319-T-C is Benign according to our data. Variant chr11-18269319-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 768434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.185 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SAA1	NM_199161.5 linkuse as main transcript	c.216T>C	p.Ala72=	synonymous_variant	3/4	ENST00000356524.9
SAA1	NM_000331.6 linkuse as main transcript	c.216T>C	p.Ala72=	synonymous_variant	3/4
SAA1	NM_001178006.3 linkuse as main transcript	c.216T>C	p.Ala72=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAA1	ENST00000356524.9 linkuse as main transcript	c.216T>C	p.Ala72=	synonymous_variant	3/4	1	NM_199161.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0742

AC:

8841

AN:

119220

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.0917

Gnomad AMR

AF:

0.0821

Gnomad ASJ

AF:

0.0486

Gnomad EAS

AF:

0.0601

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.0320

Gnomad MID

AF:

0.0508

Gnomad NFE

AF:

0.0471

Gnomad OTH

AF:

0.0711

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.155

AC:

167361

AN:

1079154

Hom.:

204

Cov.:

AF XY:

0.152

AC XY:

80584

AN XY:

528584

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.0873

Gnomad4 FIN exome

AF:

0.0545

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.0742

AC:

8855

AN:

119316

Hom.:

189

Cov.:

AF XY:

0.0727

AC XY:

4270

AN XY:

58740

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.0820

Gnomad4 ASJ

AF:

0.0486

Gnomad4 EAS

AF:

0.0606

Gnomad4 SAS

AF:

0.0198

Gnomad4 FIN

AF:

0.0320

Gnomad4 NFE

AF:

0.0471

Gnomad4 OTH

AF:

0.0702

Alfa

AF:

0.0997

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 12, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.0

DANN

Benign

0.30

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over