rs2741864

Positions:

• chr11-3670891-G-A

Variant summary

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

The NM_020402.4(CHRNA10):​c.61+361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,042 control chromosomes in the GnomAD database, including 17,188 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 0.47 (17188 hom., cov: 32)
• Consequence: CHRNA10 NM_020402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA10	NM_020402.4	c.61+361C>T		intron_variant		ENST00000250699.2	NP_065135.2
CHRNA10	NM_001303034.2	c.-620+361C>T		intron_variant			NP_001289963.1
CHRNA10	NM_001303035.2	c.-553+361C>T		intron_variant			NP_001289964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA10	ENST00000250699.2	c.61+361C>T		intron_variant		1	NM_020402.4	ENSP00000250699.2
CHRNA10	ENST00000534359.1	c.-482+361C>T		intron_variant		1		ENSP00000437107.1
CHRNA10	ENST00000526599.1	n.61+361C>T		intron_variant		1		ENSP00000432757.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71720 AN: 151924 Hom.: 17168 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.472 AC: 71791 AN: 152042 Hom.: 17188 Cov.: 32 AF XY: 0.473 AC XY: 35132 AN XY: 74302

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.490

Alfa AF: 0.467 Hom.: 5193

Bravo AF: 0.496

Asia WGS AF: 0.497 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2741864; hg19: chr11-3692121;