rs17838546

chr2-174748293-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000079.4(CHRNA1):c.1243-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,612,898 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (16 hom., cov: 32)
  • Exomes 𝑓: 0.015 (225 hom.)
• Consequence: CHRNA1 NM_000079.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-174748293-G-A is Benign according to our data. Variant chr2-174748293-G-A is described in ClinVar as [Benign]. Clinvar id is 257233.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0108 (1645/152306) while in subpopulation NFE AF= 0.0154 (1048/68042). AF 95% confidence interval is 0.0146. There are 16 homozygotes in gnomad4. There are 800 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA1	NM_000079.4	c.1243-38C>T		intron_variant		ENST00000348749.9
CHRNA1	NM_001039523.3	c.1318-38C>T		intron_variant
CHRNA1	XM_017003256.2	c.1339-38C>T		intron_variant
CHRNA1	XM_017003257.2	c.1264-38C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA1	ENST00000348749.9	c.1243-38C>T		intron_variant		1	NM_000079.4	P1
	ENST00000442996.1	n.321+18469G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1645 AN: 152188 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.0109 AC: 2713 AN: 249274 Hom.: 23 AF XY: 0.0108 AC XY: 1460 AN XY: 134946

Gnomad AFR exome AF: 0.00267

Gnomad AMR exome AF: 0.00519

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00327

Gnomad FIN exome AF: 0.0211

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.0143

GnomAD4 exome AF: 0.0154 AC: 22528 AN: 1460592 Hom.: 225 Cov.: 31 AF XY: 0.0149 AC XY: 10839 AN XY: 726622

Gnomad4 AFR exome AF: 0.00236

Gnomad4 AMR exome AF: 0.00510

Gnomad4 ASJ exome AF: 0.0165

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00302

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.0108 AC: 1645 AN: 152306 Hom.: 16 Cov.: 32 AF XY: 0.0107 AC XY: 800 AN XY: 74462

Gnomad4 AFR AF: 0.00363

Gnomad4 AMR AF: 0.00713

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00353

Gnomad4 FIN AF: 0.0222

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.0130 Hom.: 1

Bravo AF: 0.00933

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	12
Dann	Benign	0.85

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: rs17838546; hg19: chr2-175613021;