rs2305415

Positions:

• chr2-174748545-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000079.4(CHRNA1):​c.1242+35T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,606,846 control chromosomes in the GnomAD database, including 704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (277 hom., cov: 33)
  • Exomes 𝑓: 0.011 (427 hom.)
• Consequence: CHRNA1 NM_000079.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00700

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-174748545-A-T is Benign according to our data. Variant chr2-174748545-A-T is described in ClinVar as [Benign]. Clinvar id is 257232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA1	NM_000079.4	c.1242+35T>A		intron_variant		ENST00000348749.9
CHRNA1	NM_001039523.3	c.1317+35T>A		intron_variant
CHRNA1	XM_017003256.2	c.1338+35T>A		intron_variant
CHRNA1	XM_017003257.2	c.1263+35T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA1	ENST00000348749.9	c.1242+35T>A		intron_variant		1	NM_000079.4	P1
	ENST00000442996.1	n.321+18721A>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5789 AN: 152028 Hom.: 276 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00547

Gnomad OTH AF: 0.0384

GnomAD3 exomes AF: 0.0188 AC: 4663 AN: 248230 Hom.: 147 AF XY: 0.0176 AC XY: 2367 AN XY: 134204

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.0458

Gnomad SAS exome AF: 0.0222

Gnomad FIN exome AF: 0.000421

Gnomad NFE exome AF: 0.00612

Gnomad OTH exome AF: 0.0136

GnomAD4 exome AF: 0.0113 AC: 16466 AN: 1454700 Hom.: 427 Cov.: 33 AF XY: 0.0115 AC XY: 8327 AN XY: 722350

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.0636

Gnomad4 SAS exome AF: 0.0231

Gnomad4 FIN exome AF: 0.000470

Gnomad4 NFE exome AF: 0.00554

Gnomad4 OTH exome AF: 0.0160

GnomAD4 genome AF: 0.0381 AC: 5800 AN: 152146 Hom.: 277 Cov.: 33 AF XY: 0.0376 AC XY: 2798 AN XY: 74378

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.0208

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00547

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0219 Hom.: 29

Bravo AF: 0.0441

Asia WGS AF: 0.0400 AC: 140 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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.97
DANN	Benign	0.69

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: rs2305415; hg19: chr2-175613273;