rs2741862

Positions:

• chr11-3666755-G-A
• chr11-3666755-G-C
• chr11-3666755-G-T

Variant summary

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

The NM_020402.4(CHRNA10):​c.896-191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 151,950 control chromosomes in the GnomAD database, including 41,190 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 0.73 (41190 hom., cov: 31)
• Consequence: CHRNA10 NM_020402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

Genes affected

CHRNA10 (HGNC:13800): (cholinergic receptor nicotinic alpha 10 subunit) Predicted to enable acetylcholine-gated cation-selective channel activity. Acts upstream of or within positive regulation of cytosolic calcium ion concentration. Predicted to be located in membrane. Predicted to be active in cholinergic synapse and neuron projection. Predicted to be integral component of postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA10	NM_020402.4	c.896-191C>T		intron_variant		ENST00000250699.2	NP_065135.2
CHRNA10	NM_001303034.2	c.278-191C>T		intron_variant			NP_001289963.1
CHRNA10	NM_001303035.2	c.278-191C>T		intron_variant			NP_001289964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA10	ENST00000250699.2	c.896-191C>T		intron_variant		1	NM_020402.4	ENSP00000250699.2
CHRNA10	ENST00000534359.1	c.349-191C>T		intron_variant		1		ENSP00000437107.1
CHRNA10	ENST00000526599.1	n.*667-191C>T		intron_variant		1		ENSP00000432757.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111301 AN: 151832 Hom.: 41165 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.733 AC: 111378 AN: 151950 Hom.: 41190 Cov.: 31 AF XY: 0.733 AC XY: 54408 AN XY: 74244

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.742

Alfa AF: 0.758 Hom.: 12297

Bravo AF: 0.741

Asia WGS AF: 0.775 AC: 2697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.75

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: rs2741862; hg19: chr11-3687985;