chr2-174764872-T-C

Position:

• chr2-174764872-T-C

Variant summary

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

The ENST00000442996.1(ENSG00000236449):​n.322-7877T>C variant causes a intron, non coding transcript 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: ENST00000442996.1 intron, non_coding_transcript
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.116

Genes affected

(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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000442996.1	n.322-7877T>C		intron_variant, non_coding_transcript_variant		1
CHRNA1	ENST00000636168.2	c.-446-5239A>G		intron_variant		5		ENSP00000490338

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

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Lethal multiple pterygium syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 21, 2021

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;