chr11-3668953-A-T

Position:

• chr11-3668953-A-T

Variant summary

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

The ENST00000250699.2(CHRNA10):​c.362+243T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 433,702 control chromosomes in the GnomAD database, including 94,570 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 0.62 (30255 hom., cov: 31)
  • Exomes 𝑓: 0.67 (64315 hom.)
• Consequence: CHRNA10 ENST00000250699.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA10	NM_020402.4	c.362+243T>A		intron_variant		ENST00000250699.2	NP_065135.2
CHRNA10	NM_001303034.2	c.-257+243T>A		intron_variant			NP_001289963.1
CHRNA10	NM_001303035.2	c.-257+243T>A		intron_variant			NP_001289964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA10	ENST00000250699.2	c.362+243T>A		intron_variant		1	NM_020402.4	ENSP00000250699	P1
CHRNA10	ENST00000534359.1	c.-186+243T>A		intron_variant		1		ENSP00000437107
CHRNA10	ENST00000526599.1	c.*133+243T>A		intron_variant, NMD_transcript_variant		1		ENSP00000432757
CHRNA10	ENST00000493827.2	n.552T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94364 AN: 151884 Hom.: 30240 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.643

GnomAD4 exome AF: 0.671 AC: 189023 AN: 281700 Hom.: 64315 Cov.: 3 AF XY: 0.670 AC XY: 97413 AN XY: 145392

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.733

Gnomad4 EAS exome AF: 0.677

Gnomad4 SAS exome AF: 0.622

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.672

GnomAD4 genome AF: 0.621 AC: 94425 AN: 152002 Hom.: 30255 Cov.: 31 AF XY: 0.621 AC XY: 46110 AN XY: 74308

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.640

Alfa AF: 0.637 Hom.: 3918

Bravo AF: 0.629

Asia WGS AF: 0.663 AC: 2307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.40
DANN	Benign	0.82

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: rs2741868; hg19: chr11-3690183;