NM_020402.4:c.896-191C>T

Variant names:

• chr11-3666755-G-A
• rs2741862
• NM_020402.4:c.896-191C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHRNA10	NM_020402.4	c.896-191C>T		intron_variant	Intron 4 of 4	ENST00000250699.2	NP_065135.2
CHRNA10	NM_001303034.2	c.278-191C>T		intron_variant	Intron 4 of 4		NP_001289963.1
CHRNA10	NM_001303035.2	c.278-191C>T		intron_variant	Intron 4 of 4		NP_001289964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA10	ENST00000250699.2	c.896-191C>T		intron_variant	Intron 4 of 4	1	NM_020402.4	ENSP00000250699.2
CHRNA10	ENST00000534359.1	c.349-191C>T		intron_variant	Intron 4 of 4	1		ENSP00000437107.1
CHRNA10	ENST00000526599.1	n.*667-191C>T		intron_variant	Intron 4 of 4	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

African (AFR) AF: 0.648 AC: 26870 AN: 41446

American (AMR) AF: 0.836 AC: 12763 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2838 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3780 AN: 5134

South Asian (SAS) AF: 0.800 AC: 3848 AN: 4810

European-Finnish (FIN) AF: 0.679 AC: 7158 AN: 10548

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51619 AN: 67950

Other (OTH) AF: 0.742 AC: 1568 AN: 2114

Alfa AF: 0.758 Hom.: 20823

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
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2741862; hg19: chr11-3687985;