Variant rs74533173 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000348749.9(CHRNA1):c.621C>T(p.Ser207=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,614,108 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

CHRNA1
ENST00000348749.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.70

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 2-174753660-G-A is Benign according to our data. Variant chr2-174753660-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 383111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.7 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00172 (262/152214) while in subpopulation AFR AF= 0.0058 (241/41536). AF 95% confidence interval is 0.0052. There are 3 homozygotes in gnomad4. There are 112 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHRNA1	NM_000079.4 linkuse as main transcript	c.621C>T	p.Ser207=	synonymous_variant	6/9	ENST00000348749.9	NP_000070.1
CHRNA1	NM_001039523.3 linkuse as main transcript	c.696C>T	p.Ser232=	synonymous_variant	7/10		NP_001034612.1
CHRNA1	XM_017003256.2 linkuse as main transcript	c.717C>T	p.Ser239=	synonymous_variant	6/9		XP_016858745.1
CHRNA1	XM_017003257.2 linkuse as main transcript	c.642C>T	p.Ser214=	synonymous_variant	5/8		XP_016858746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9 linkuse as main transcript	c.621C>T	p.Ser207=	synonymous_variant	6/9	1	NM_000079.4	ENSP00000261008	P1	P02708-2
	ENST00000442996.1 linkuse as main transcript	n.322-19089G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

258

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00572

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000501

AC:

126

AN:

251382

Hom.:

AF XY:

0.000339

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00535

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000220

AC:

322

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00582

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.00172

AC:

262

AN:

152214

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

112

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00580

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000736

Hom.:

Bravo

AF:

0.00178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2019	- -

Lethal multiple pterygium syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.5

DANN

Benign

0.87

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