2-174764872-T-C

Variant names:

• chr2-174764872-T-C
• rs16862847
• ENST00000442996.1:n.322-7877T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000636168.2(CHRNA1):​c.-446-5239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,176 control chromosomes in the GnomAD database, including 1,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.14 (1555 hom., cov: 32)
• Consequence: CHRNA1 ENST00000636168.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.116

Genes affected

ENSG00000236449 (HGNC:):

CHRNA1 (HGNC:1955): (cholinergic receptor nicotinic alpha 1 subunit) The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-174764872-T-C is Benign according to our data. Variant chr2-174764872-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 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
ENSG00000236449	ENST00000442996.1	n.322-7877T>C		intron_variant	Intron 3 of 3	1
CHRNA1	ENST00000636168.2	c.-446-5239A>G		intron_variant	Intron 2 of 9	5		ENSP00000490338.2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20585 AN: 152058 Hom.: 1553 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.135 AC: 20610 AN: 152176 Hom.: 1555 Cov.: 32 AF XY: 0.134 AC XY: 9952 AN XY: 74406

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0885

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.145

Alfa AF: 0.139 Hom.: 351

Bravo AF: 0.135

Asia WGS AF: 0.185 AC: 640 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lethal multiple pterygium syndrome Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 25910213, 17687331) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
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: rs16862847; hg19: chr2-175629600;