dbSNP rs3014837: S100A7:p.Glu28Asp (chr1-153458930-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

31 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
S100A7	NM_002963.4 link	c.84G>C	p.Glu28Asp	missense_variant	Exon 2 of 3	ENST00000368723.4	NP_002954.2	P31151

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A7	ENST00000368723.4 link	c.84G>C	p.Glu28Asp	missense_variant	Exon 2 of 3	1	NM_002963.4	ENSP00000357712.3		P31151
S100A7	ENST00000368722.5 link	c.84G>C	p.Glu28Asp	missense_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.962

AC:

241668

AN:

251244

AF XY:

0.961

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 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

African (AFR)

AF:

0.989

AC:

33056

AN:

33408

American (AMR)

AF:

0.976

AC:

43629

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.961

AC:

25053

AN:

26076

East Asian (EAS)

AF:

1.00

AC:

39691

AN:

39700

South Asian (SAS)

AF:

0.977

AC:

83766

AN:

85740

European-Finnish (FIN)

AF:

0.964

AC:

51483

AN:

53418

Middle Eastern (MID)

AF:

0.984

AC:

5638

AN:

5732

European-Non Finnish (NFE)

AF:

0.945

AC:

1050398

AN:

1111656

Other (OTH)

AF:

0.958

AC:

57780

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

3753

7506

11258

15011

18764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21602

43204

64806

86408

108010

<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:

0.965

AC:

146894

AN:

152228

Hom.:

70910

Cov.:

AF XY:

0.966

AC XY:

71913

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.991

AC:

41169

AN:

41550

American (AMR)

AF:

0.971

AC:

14839

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.965

AC:

3336

AN:

3458

East Asian (EAS)

AF:

1.00

AC:

5172

AN:

5174

South Asian (SAS)

AF:

0.980

AC:

4715

AN:

4812

European-Finnish (FIN)

AF:

0.967

AC:

10258

AN:

10610

Middle Eastern (MID)

AF:

0.976

AC:

287

AN:

294

European-Non Finnish (NFE)

AF:

0.944

AC:

64201

AN:

68018

Other (OTH)

AF:

0.959

AC:

2026

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

272

544

816

1088

1360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.950

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

(source)

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

PhyloP100

0.21

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

Mutation Taster

=100/0

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