2-174759379-GAA-GAAA

Position:

• chr2-174759379-GAA-GAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000079.4(CHRNA1):​c.190-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: CHRNA1 NM_000079.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.810

Genes affected

CHRNA1 (HGNC:1955): (cholinergic receptor nicotinic alpha 1 subunit) The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012]

ENSG00000236449 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 2-174759379-G-GA is Benign according to our data. Variant chr2-174759379-G-GA is described in ClinVar as [Benign]. Clinvar id is 772712.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA1	NM_000079.4	c.190-5dupT		splice_region_variant, intron_variant		ENST00000348749.9	NP_000070.1
CHRNA1	NM_001039523.3	c.190-5dupT		splice_region_variant, intron_variant			NP_001034612.1
CHRNA1	XM_017003256.2	c.211-5dupT		splice_region_variant, intron_variant			XP_016858745.1
CHRNA1	XM_017003257.2	c.211-5dupT		splice_region_variant, intron_variant			XP_016858746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9	c.190-5dupT		splice_region_variant, intron_variant		1	NM_000079.4	ENSP00000261008.5

Frequencies

GnomAD3 genomes AF: 0.0000397 AC: 6 AN: 151160 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000590

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000199 AC: 29 AN: 1458952 Hom.: 0 Cov.: 0 AF XY: 0.0000138 AC XY: 10 AN XY: 725968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome AF: 0.0000397 AC: 6 AN: 151160 Hom.: 0 Cov.: 0 AF XY: 0.0000542 AC XY: 4 AN XY: 73756

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000590

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lethal multiple pterygium syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

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: rs34695580; hg19: chr2-175624107;