chr2-174747698-G-T

Position:

chr2-174747698-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000079.4(CHRNA1):c.*426C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 214,352 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 2 hom. )

Consequence

CHRNA1
NM_000079.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.167

Variant links:

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]

CHRNA1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-174747698-G-T is Benign according to our data. Variant chr2-174747698-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 332428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00716 (1090/152208) while in subpopulation AFR AF= 0.0256 (1063/41514). AF 95% confidence interval is 0.0243. There are 11 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA1	NM_000079.4 link	c.*426C>A	3_prime_UTR_variant	9/9	ENST00000348749.9	NP_000070.1	P02708-2Q53SH4
CHRNA1	NM_001039523.3 link	c.*426C>A	3_prime_UTR_variant	10/10		NP_001034612.1	P02708-1Q53SH4
CHRNA1	XM_017003256.2 link	c.*426C>A	3_prime_UTR_variant	9/9		XP_016858745.1
CHRNA1	XM_017003257.2 link	c.*426C>A	3_prime_UTR_variant	8/8		XP_016858746.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHRNA1	ENST00000348749 link	c.*426C>A	3_prime_UTR_variant	9/9	1	NM_000079.4	ENSP00000261008.5	P02708-2
ENSG00000236449	ENST00000442996.1 link	n.321+17874G>T	intron_variant		1
CHRNA1	ENST00000261007 link	c.*426C>A	3_prime_UTR_variant	10/10	2		ENSP00000261007.5	P02708-1
CHRNA1	ENST00000672640 link	c.*426C>A	3_prime_UTR_variant	10/10			ENSP00000500507.1	A0A1B0GV17

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

1087

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD4 exome

AF:

0.000756

AC:

AN:

62144

Hom.:

Cov.:

AF XY:

0.000736

AC XY:

AN XY:

32606

show subpopulations

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00716

AC:

1090

AN:

152208

Hom.:

Cov.:

AF XY:

0.00687

AC XY:

511

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0256

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00598

Hom.:

Bravo

AF:

0.00853

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Lethal multiple pterygium syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2021

- -

Congenital myasthenic syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.5

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over