rs3795391

Variant names:

• chr1-153390629-T-C
• rs3795391
• NM_002964.5:c.-22-72A>G

Variant summary

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

The NM_002964.5(S100A8):​c.-22-72A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,560,056 control chromosomes in the GnomAD database, including 9,360 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 0.084 (619 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8741 hom.)
• Consequence: S100A8 NM_002964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 19 publications found

Genes affected

S100A8 (HGNC:10498): (S100 calcium binding protein A8) 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 may function in the inhibition of casein kinase and as a cytokine. Altered expression of this protein is associated with the disease cystic fibrosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002964.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A8	NM_002964.5	MANE Select	c.-22-72A>G		intron	N/A	NP_002955.2
	S100A8	NM_001319196.1		c.34-55A>G		intron	N/A	NP_001306125.1
	S100A8	NM_001319197.1		c.34-58A>G		intron	N/A	NP_001306126.1	P05109

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A8	ENST00000368733.4	TSL:1 MANE Select	c.-22-72A>G		intron	N/A	ENSP00000357722.3	P05109
	S100A8	ENST00000477801.1	TSL:1	n.443A>G		non_coding_transcript_exon	Exon 1 of 2
	S100A8	ENST00000955443.1		c.-94A>G		5_prime_UTR	Exon 2 of 3	ENSP00000625502.1

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12748 AN: 152098 Hom.: 619 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0864

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0930

GnomAD4 exome AF: 0.110 AC: 154537 AN: 1407840 Hom.: 8741 Cov.: 25 AF XY: 0.110 AC XY: 76792 AN XY: 697284

African (AFR) AF: 0.0233 AC: 757 AN: 32476

American (AMR) AF: 0.0875 AC: 3680 AN: 42074

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 2201 AN: 23298

East Asian (EAS) AF: 0.0905 AC: 3563 AN: 39354

South Asian (SAS) AF: 0.104 AC: 8283 AN: 79776

European-Finnish (FIN) AF: 0.0920 AC: 4170 AN: 45310

Middle Eastern (MID) AF: 0.0976 AC: 541 AN: 5542

European-Non Finnish (NFE) AF: 0.116 AC: 125181 AN: 1081574

Other (OTH) AF: 0.105 AC: 6161 AN: 58436

GnomAD4 genome AF: 0.0838 AC: 12752 AN: 152216 Hom.: 619 Cov.: 32 AF XY: 0.0831 AC XY: 6186 AN XY: 74416

African (AFR) AF: 0.0263 AC: 1093 AN: 41556

American (AMR) AF: 0.0864 AC: 1321 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3470

East Asian (EAS) AF: 0.0945 AC: 488 AN: 5164

South Asian (SAS) AF: 0.100 AC: 483 AN: 4814

European-Finnish (FIN) AF: 0.0886 AC: 939 AN: 10598

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7770 AN: 68006

Other (OTH) AF: 0.0963 AC: 203 AN: 2108

Alfa AF: 0.0973 Hom.: 117

Bravo AF: 0.0831

Asia WGS AF: 0.0760 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.027
DANN	Benign	0.43
PhyloP100		-3.1
PromoterAI		-0.0087	Neutral
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: rs3795391; hg19: chr1-153363105; COSMIC: COSV64198070;