rs6730111

Positions:

• chr2-174762447-A-C

Variant summary

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

The NM_000079.4(CHRNA1):​c.43+1905T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,314 control chromosomes in the GnomAD database, including 1,261 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 0.075 (1261 hom., cov: 33)
• Consequence: CHRNA1 NM_000079.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA1	NM_000079.4	c.43+1905T>G		intron_variant		ENST00000348749.9
CHRNA1	NM_001039523.3	c.43+1905T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA1	ENST00000348749.9	c.43+1905T>G		intron_variant		1	NM_000079.4	P1
	ENST00000442996.1	n.322-10302A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11336 AN: 152196 Hom.: 1256 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00611

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0747 AC: 11377 AN: 152314 Hom.: 1261 Cov.: 33 AF XY: 0.0731 AC XY: 5448 AN XY: 74478

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00611

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0513 Hom.: 111

Bravo AF: 0.0850

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6730111; hg19: chr2-175627175;