chr11-3668953-A-G

Variant names:

• chr11-3668953-A-G
• rs2741868
• NM_020402.4:c.362+243T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020402.4(CHRNA10):​c.362+243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRNA10 NM_020402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020402.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA10	NM_020402.4	MANE Select	c.362+243T>C		intron	N/A	NP_065135.2
	CHRNA10	NM_001303034.2		c.-257+243T>C		intron	N/A	NP_001289963.1
	CHRNA10	NM_001303035.2		c.-257+243T>C		intron	N/A	NP_001289964.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA10	ENST00000250699.2	TSL:1 MANE Select	c.362+243T>C		intron	N/A	ENSP00000250699.2
	CHRNA10	ENST00000534359.1	TSL:1	c.-186+243T>C		intron	N/A	ENSP00000437107.1
	CHRNA10	ENST00000526599.1	TSL:1	n.*133+243T>C		intron	N/A	ENSP00000432757.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 282652 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 145870

African (AFR) AF: 0.00 AC: 0 AN: 8564

American (AMR) AF: 0.00 AC: 0 AN: 10548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9560

East Asian (EAS) AF: 0.00 AC: 0 AN: 20350

South Asian (SAS) AF: 0.00 AC: 0 AN: 21754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1364

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 174304

Other (OTH) AF: 0.00 AC: 0 AN: 17604

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.76
PhyloP100		-1.1

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: rs2741868; hg19: chr11-3690183;