rs7129556

Variant names:

• chr11-77589003-C-T
• rs7129556
• ENST00000526761.5:n.*156-3544G>A

Variant summary

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

The ENST00000526761.5(CLNS1A):​n.*156-3544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,192 control chromosomes in the GnomAD database, including 3,886 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 0.22 (3886 hom., cov: 32)
• Consequence: CLNS1A ENST00000526761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715
• Publications: 15 publications found

Genes affected

CLNS1A (HGNC:2080): (chloride nucleotide-sensitive channel 1A) This gene encodes a protein that functions in multiple regulatory pathways. The encoded protein complexes with numerous cytosolic proteins and performs diverse functions including regulation of small nuclear ribonucleoprotein biosynthesis, platelet activation and cytoskeletal organization. The protein is also found associated with the plasma membrane where it functions as a chloride current regulator. Pseudogenes of this gene are found on chromosomes 1, 4 and 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLNS1A	ENST00000526761.5	n.*156-3544G>A		intron_variant	Intron 3 of 5	3		ENSP00000475218.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33460 AN: 152074 Hom.: 3888 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.228

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.220 AC: 33468 AN: 152192 Hom.: 3886 Cov.: 32 AF XY: 0.216 AC XY: 16088 AN XY: 74414

African (AFR) AF: 0.172 AC: 7143 AN: 41536

American (AMR) AF: 0.193 AC: 2944 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1015 AN: 3472

East Asian (EAS) AF: 0.111 AC: 576 AN: 5184

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2063 AN: 10588

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17974 AN: 67992

Other (OTH) AF: 0.225 AC: 476 AN: 2112

Alfa AF: 0.250 Hom.: 19663

Bravo AF: 0.219

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.65
PhyloP100		0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7129556; hg19: chr11-77300048; COSMIC: COSV57993274;