rs7129556

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.225

Alfa AF: 0.256 Hom.: 8943

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

Splicing

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

Publications

LitVar

Other links and lift over

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