rs886348487

Variant names:

• chr1-154572164-G-C
• NM_000748.3:c.1338+3G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-154572164-G-C
• chr1-154572164-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000748.3(CHRNB2):​c.1338+3G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,384,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CHRNB2 NM_000748.3 splice_region, intron
• Scores: Splicing: ADA: 0.9955
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768

Genes affected

CHRNB2 (HGNC:1962): (cholinergic receptor nicotinic beta 2 subunit) Neuronal acetylcholine receptors are homo- or heteropentameric complexes composed of homologous alpha and beta subunits. They belong to a superfamily of ligand-gated ion channels which allow the flow of sodium and potassium across the plasma membrane in response to ligands such as acetylcholine and nicotine. This gene encodes one of several beta subunits. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.1338+3G>C		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000368476.4	NP_000739.1
CHRNB2	XM_017000180.3	c.828+3G>C		splice_region_variant, intron_variant	Intron 2 of 2		XP_016855669.1
CHRNB2	XR_001736952.3	n.1605+3G>C		splice_region_variant, intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4	c.1338+3G>C		splice_region_variant, intron_variant	Intron 5 of 5	1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000637900.1	c.1344+3G>C		splice_region_variant, intron_variant	Intron 5 of 5	5		ENSP00000490474.1
CHRNB2	ENST00000636034.1	n.1338+3G>C		splice_region_variant, intron_variant	Intron 5 of 8	5		ENSP00000489703.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1384574 Hom.: 0 Cov.: 33 AF XY: 0.00000293 AC XY: 2 AN XY: 683344

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.79
SpliceAI score (max)		0.83		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.83		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154544640;