2-174772073-A-G

Variant names:

• chr2-174772073-A-G
• rs935863
• ENST00000442996.1:n.322-676A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636168.2(CHRNA1):​c.-447+4032T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,986 control chromosomes in the GnomAD database, including 12,659 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 0.40 (12659 hom., cov: 32)
• Consequence: CHRNA1 ENST00000636168.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 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.322-676A>G		intron_variant	Intron 3 of 3	1
CHRNA1	ENST00000636168.2	c.-447+4032T>C		intron_variant	Intron 2 of 9	5		ENSP00000490338.2
ENSG00000236449	ENST00000654673.1	n.285A>G		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60824 AN: 151868 Hom.: 12643 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.401 AC: 60883 AN: 151986 Hom.: 12659 Cov.: 32 AF XY: 0.408 AC XY: 30318 AN XY: 74272

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.370

Alfa AF: 0.345 Hom.: 11506

Bravo AF: 0.404

Asia WGS AF: 0.541 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs935863; hg19: chr2-175636801;