rs150689366

Positions:

• chr2-174748849-AATT-A

Variant summary

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

The NM_000079.4(CHRNA1):​c.1003-33_1003-31del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,612,100 control chromosomes in the GnomAD database, including 226 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (102 hom.)
• Consequence: CHRNA1 NM_000079.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.81

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-174748849-AATT-A is Benign according to our data. Variant chr2-174748849-AATT-A is described in ClinVar as [Benign]. Clinvar id is 257231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA1	NM_000079.4	c.1003-33_1003-31del		intron_variant		ENST00000348749.9	NP_000070.1
CHRNA1	NM_001039523.3	c.1078-33_1078-31del		intron_variant			NP_001034612.1
CHRNA1	XM_017003256.2	c.1099-33_1099-31del		intron_variant			XP_016858745.1
CHRNA1	XM_017003257.2	c.1024-33_1024-31del		intron_variant			XP_016858746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9	c.1003-33_1003-31del		intron_variant		1	NM_000079.4	ENSP00000261008	P1
	ENST00000442996.1	n.321+19029_321+19031del		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3407 AN: 152158 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00897

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00556 AC: 1369 AN: 246436 Hom.: 49 AF XY: 0.00413 AC XY: 552 AN XY: 133578

Gnomad AFR exome AF: 0.0771

Gnomad AMR exome AF: 0.00334

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000127

Gnomad OTH exome AF: 0.000826

GnomAD4 exome AF: 0.00211 AC: 3086 AN: 1459824 Hom.: 102 AF XY: 0.00179 AC XY: 1301 AN XY: 726322

Gnomad4 AFR exome AF: 0.0770

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000818

Gnomad4 OTH exome AF: 0.00381

GnomAD4 genome AF: 0.0224 AC: 3414 AN: 152276 Hom.: 124 Cov.: 32 AF XY: 0.0221 AC XY: 1646 AN XY: 74468

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00961 Hom.: 6

Bravo AF: 0.0247

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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: rs150689366; hg19: chr2-175613577;