Variant rs3014837 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002963.4(S100A7):c.84G>C(p.Glu28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 1,613,000 control chromosomes in the GnomAD database, including 732,899 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.96 ( 70910 hom., cov: 31)

Exomes 𝑓: 0.95 ( 661989 hom. )

Consequence

S100A7
NM_002963.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.214

Variant links:

Genes affected

S100A7 (HGNC:10497): (S100 calcium binding protein A7) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein differs from the other S100 proteins of known structure in its lack of calcium binding ability in one EF-hand at the N-terminus. The protein is overexpressed in hyperproliferative skin diseases, exhibits antimicrobial activities against bacteria and induces immunomodulatory activities. [provided by RefSeq, Nov 2014]

S100A7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0377497E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A7	NM_002963.4 link	c.84G>C	p.Glu28Asp	missense_variant	2/3	ENST00000368723.4	NP_002954.2	P31151

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100A7	ENST00000368723.4 link	c.84G>C	p.Glu28Asp	missense_variant	2/3	1	NM_002963.4	ENSP00000357712.3		P31151
S100A7	ENST00000368722.5 link	c.84G>C	p.Glu28Asp	missense_variant	2/3	3		ENSP00000357711.1		P31151

Frequencies

GnomAD3 genomes

AF:

0.965

AC:

146775

AN:

152110

Hom.:

70850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.991

Gnomad AMI

AF:

0.977

Gnomad AMR

AF:

0.971

Gnomad ASJ

AF:

0.965

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.980

Gnomad FIN

AF:

0.967

Gnomad MID

AF:

0.975

Gnomad NFE

AF:

0.944

Gnomad OTH

AF:

0.958

GnomAD3 exomes

AF:

0.962

AC:

241668

AN:

251244

Hom.:

116289

AF XY:

0.961

AC XY:

130494

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.985

Gnomad AMR exome

AF:

0.977

Gnomad ASJ exome

AF:

0.961

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.978

Gnomad FIN exome

AF:

0.965

Gnomad NFE exome

AF:

0.944

Gnomad OTH exome

AF:

0.952

GnomAD4 exome

AF:

0.952

AC:

1390494

AN:

1460772

Hom.:

661989

Cov.:

AF XY:

0.952

AC XY:

691993

AN XY:

726608

show subpopulations

Gnomad4 AFR exome

AF:

0.989

Gnomad4 AMR exome

AF:

0.976

Gnomad4 ASJ exome

AF:

0.961

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.977

Gnomad4 FIN exome

AF:

0.964

Gnomad4 NFE exome

AF:

0.945

Gnomad4 OTH exome

AF:

0.958

GnomAD4 genome

AF:

0.965

AC:

146894

AN:

152228

Hom.:

70910

Cov.:

AF XY:

0.966

AC XY:

71913

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.991

Gnomad4 AMR

AF:

0.971

Gnomad4 ASJ

AF:

0.965

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.980

Gnomad4 FIN

AF:

0.967

Gnomad4 NFE

AF:

0.944

Gnomad4 OTH

AF:

0.959

Alfa

AF:

0.950

Hom.:

22255

Bravo

AF:

0.966

TwinsUK

AF:

0.948

AC:

3515

ALSPAC

AF:

0.945

AC:

3642

ESP6500AA

AF:

0.985

AC:

4341

ESP6500EA

AF:

0.944

AC:

8118

ExAC

AF:

0.961

AC:

116660

Asia WGS

AF:

0.992

AC:

3451

AN:

3478

EpiCase

AF:

0.947

EpiControl

AF:

0.946

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.037

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.64

DANN

Benign

0.089

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00018

LIST_S2

Benign

0.12

.;T

MetaRNN

Benign

0.0000020

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.3

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.018

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.026

MutPred

0.16

Loss of methylation at K29 (P = 0.0811);Loss of methylation at K29 (P = 0.0811);

MPC

0.034

ClinPred

0.00016

GERP RS

-0.42

Varity_R

0.033

gMVP

0.13

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