rs10629807

Variant names:

• chr2-174763827-T-TTC
• rs10629807
• NM_000079.4:c.43+524_43+525insGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000079.4(CHRNA1):​c.43+524_43+525insGA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51573 hom., cov: 0)
• Consequence: CHRNA1 NM_000079.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 1A

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• lethal multiple pterygium syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• myasthenic syndrome, congenital, 1B, fast-channel

  Inheritance: AR, AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000236449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000079.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA1	NM_000079.4	MANE Select	c.43+524_43+525insGA		intron	N/A	NP_000070.1
	CHRNA1	NM_001039523.3		c.43+524_43+525insGA		intron	N/A	NP_001034612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA1	ENST00000348749.9	TSL:1 MANE Select	c.43+524_43+525insGA		intron	N/A	ENSP00000261008.5
	CHRNA1	ENST00000409323.1	TSL:1	c.43+524_43+525insGA		intron	N/A	ENSP00000386684.1
	ENSG00000236449	ENST00000442996.1	TSL:1	n.322-8922_322-8921insTC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124032 AN: 151804 Hom.: 51551 Cov.: 0

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.822

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.817 AC: 124104 AN: 151922 Hom.: 51573 Cov.: 0 AF XY: 0.820 AC XY: 60895 AN XY: 74250

African (AFR) AF: 0.655 AC: 27095 AN: 41364

American (AMR) AF: 0.888 AC: 13583 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2926 AN: 3464

East Asian (EAS) AF: 0.942 AC: 4877 AN: 5178

South Asian (SAS) AF: 0.750 AC: 3597 AN: 4798

European-Finnish (FIN) AF: 0.932 AC: 9856 AN: 10572

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.875 AC: 59422 AN: 67944

Other (OTH) AF: 0.817 AC: 1720 AN: 2104

Alfa AF: 0.826 Hom.: 5619

Asia WGS AF: 0.801 AC: 2786 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10629807; hg19: chr2-175628555;