1-153458724-T-C

Variant names:

• chr1-153458724-T-C
• rs3014836
• NM_002963.4:c.141+149A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002963.4(S100A7):​c.141+149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,204 control chromosomes in the GnomAD database, including 56,704 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 0.86 (56704 hom., cov: 31)
  • Exomes 𝑓: 0.81 (224543 hom.)
  • Failed GnomAD Quality Control
• Consequence: S100A7 NM_002963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A7	NM_002963.4	c.141+149A>G		intron_variant	Intron 2 of 2	ENST00000368723.4	NP_002954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A7	ENST00000368723.4	c.141+149A>G		intron_variant	Intron 2 of 2	1	NM_002963.4	ENSP00000357712.3
S100A7	ENST00000368722.5	c.141+149A>G		intron_variant	Intron 2 of 2	3		ENSP00000357711.1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130840 AN: 152086 Hom.: 56630 Cov.: 31

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.844

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.814 AC: 547616 AN: 672456 Hom.: 224543 AF XY: 0.809 AC XY: 279903 AN XY: 345956

African (AFR) AF: 0.942 AC: 15508 AN: 16466

American (AMR) AF: 0.839 AC: 17438 AN: 20794

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 11977 AN: 14892

East Asian (EAS) AF: 0.721 AC: 24289 AN: 33690

South Asian (SAS) AF: 0.706 AC: 35783 AN: 50668

European-Finnish (FIN) AF: 0.905 AC: 34994 AN: 38650

Middle Eastern (MID) AF: 0.707 AC: 1694 AN: 2396

European-Non Finnish (NFE) AF: 0.820 AC: 378778 AN: 461826

Other (OTH) AF: 0.821 AC: 27155 AN: 33074

GnomAD4 genome AF: 0.861 AC: 130975 AN: 152204 Hom.: 56704 Cov.: 31 AF XY: 0.860 AC XY: 63966 AN XY: 74420

African (AFR) AF: 0.943 AC: 39164 AN: 41520

American (AMR) AF: 0.838 AC: 12808 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2816 AN: 3472

East Asian (EAS) AF: 0.743 AC: 3851 AN: 5184

South Asian (SAS) AF: 0.700 AC: 3375 AN: 4824

European-Finnish (FIN) AF: 0.910 AC: 9663 AN: 10616

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56520 AN: 67996

Other (OTH) AF: 0.846 AC: 1779 AN: 2104

Alfa AF: 0.859 Hom.: 7006

Bravo AF: 0.860

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.74
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3014836; hg19: chr1-153431200; COSMIC: COSV64193135;