1-153458959-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002963.4(S100A7):c.55A>C(p.Lys19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,614,090 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (20 hom.)
• Consequence: S100A7 NM_002963.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.162

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0136656165).
• BP6: Variant 1-153458959-T-G is Benign according to our data. Variant chr1-153458959-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00452 (6605/1461766) while in subpopulation MID AF= 0.0186 (107/5764). AF 95% confidence interval is 0.0157. There are 20 homozygotes in gnomad4_exome. There are 3277 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S100A7	NM_002963.4	c.55A>C	p.Lys19Gln	missense_variant	2/3	ENST00000368723.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S100A7	ENST00000368723.4	c.55A>C	p.Lys19Gln	missense_variant	2/3	1	NM_002963.4	P1
S100A7	ENST00000368722.5	c.55A>C	p.Lys19Gln	missense_variant	2/3	3		P1

Frequencies

GnomAD3 genomes AF: 0.00379 AC: 577 AN: 152206 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00578

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00397 AC: 997 AN: 251356 Hom.: 2 AF XY: 0.00394 AC XY: 535 AN XY: 135844

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00486

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00471

Gnomad NFE exome AF: 0.00580

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00452 AC: 6605 AN: 1461766 Hom.: 20 Cov.: 34 AF XY: 0.00451 AC XY: 3277 AN XY: 727188

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.00478

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00125

Gnomad4 FIN exome AF: 0.00563

Gnomad4 NFE exome AF: 0.00498

Gnomad4 OTH exome AF: 0.00417

GnomAD4 genome AF: 0.00379 AC: 578 AN: 152324 Hom.: 2 Cov.: 32 AF XY: 0.00342 AC XY: 255 AN XY: 74488

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00546

Gnomad4 NFE AF: 0.00578

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00514 Hom.: 1

Bravo AF: 0.00345

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00605 AC: 52

ExAC AF: 0.00444 AC: 539

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.00643

EpiControl AF: 0.00676

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

S100A7: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	13
Dann	Benign	0.59
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0034	N
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.014	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.59	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.022
Sift	Benign	0.82	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.073	B;B
Vest4		0.11
MVP		0.50
MPC		0.050
ClinPred		0.0019	T
GERP RS		-0.49
Varity_R		0.18
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs72708760; hg19: chr1-153431435;