2-174759379-GAA-GA

Position:

• chr2-174759379-GAA-GA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000079.4(CHRNA1):​c.190-5delT 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 0.36 (11521 hom., cov: 0)
  • Exomes 𝑓: 0.45 (152651 hom.)
• Consequence: CHRNA1 NM_000079.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• 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 Benign. Variant got -16 ACMG points.

• BP6: Variant 2-174759379-GA-G is Benign according to our data. Variant chr2-174759379-GA-G is described in ClinVar as [Benign]. Clinvar id is 257235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-174759379-GA-G is described in Lovd as [Benign]. Variant chr2-174759379-GA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA1	NM_000079.4	c.190-5delT		splice_region_variant, intron_variant		ENST00000348749.9	NP_000070.1
CHRNA1	NM_001039523.3	c.190-5delT		splice_region_variant, intron_variant			NP_001034612.1
CHRNA1	XM_017003256.2	c.211-5delT		splice_region_variant, intron_variant			XP_016858745.1
CHRNA1	XM_017003257.2	c.211-5delT		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.190-5delT		splice_region_variant, intron_variant		1	NM_000079.4	ENSP00000261008.5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53733 AN: 151090 Hom.: 11528 Cov.: 0

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.408

GnomAD3 exomes AF: 0.408 AC: 101884 AN: 249652 Hom.: 22643 AF XY: 0.411 AC XY: 55439 AN XY: 135028

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.409

Gnomad ASJ exome AF: 0.545

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.485

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.455

GnomAD4 exome AF: 0.449 AC: 654943 AN: 1459282 Hom.: 152651 Cov.: 0 AF XY: 0.445 AC XY: 322872 AN XY: 726120

Gnomad4 AFR exome AF: 0.0956

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.355 AC: 53729 AN: 151206 Hom.: 11521 Cov.: 0 AF XY: 0.352 AC XY: 26027 AN XY: 73854

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.405

Alfa AF: 0.358 Hom.: 1733

Bravo AF: 0.343

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Lethal multiple pterygium syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Autosomal recessive multiple pterygium syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Myasthenic syndrome, congenital, 1B, fast-channel Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Congenital Myasthenic Syndrome, Dominant/Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 29, 2018

- -

Congenital myasthenic syndrome 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs34695580; hg19: chr2-175624107;