17-7445169-GGC-AA

Variant names:

• chr17-7445169-GGC-AA
• NM_000747.3:c.42_44delGGCinsAA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000747.3(CHRNB1):​c.42_44delGGCinsAA​(p.Ala15SerfsTer52) variant causes a frameshift, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHRNB1 NM_000747.3 frameshift, missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.915
• Publications: 0 publications found

Genes affected

CHRNB1 (HGNC:1961): (cholinergic receptor nicotinic beta 1 subunit) The muscle acetylcholine receptor is composed of five subunits: two alpha subunits and one beta, one gamma, and one delta subunit. This gene encodes the beta subunit of the acetylcholine receptor. The acetylcholine receptor changes conformation upon acetylcholine binding leading to the opening of an ion-conducting channel across the plasma membrane. Mutations in this gene are associated with slow-channel congenital myasthenic syndrome. [provided by RefSeq, Jul 2008]

ENSG00000272884 (HGNC:):

FGF11 (HGNC:3667): (fibroblast growth factor 11) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The function of this gene has not yet been determined. The expression pattern of the mouse homolog implies a role in nervous system development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 27 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-7445169-GGC-AA is Pathogenic according to our data. Variant chr17-7445169-GGC-AA is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1321823.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000747.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB1	NM_000747.3	MANE Select	c.42_44delGGCinsAA	p.Ala15SerfsTer52	frameshift missense	Exon 1 of 11	NP_000738.2
	FGF11	NM_004112.4	MANE Select	c.*2023_*2025delGGCinsAA		downstream_gene	N/A	NP_004103.1	Q92914
	FGF11	NM_001303460.2		c.*2023_*2025delGGCinsAA		downstream_gene	N/A	NP_001290389.1	B7Z1C3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB1	ENST00000306071.7	TSL:1 MANE Select	c.42_44delGGCinsAA	p.Ala15SerfsTer52	frameshift missense	Exon 1 of 11	ENSP00000304290.2	P11230-1
	ENSG00000272884	ENST00000575331.1	TSL:1	n.4756_4758delGGCinsAA		non_coding_transcript_exon	Exon 3 of 3
	CHRNB1	ENST00000572857.5	TSL:4	c.42_44delGGCinsAA	p.Ala15SerfsTer52	frameshift missense	Exon 1 of 6	ENSP00000461402.1	I3L4N5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.92

Splicing

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

Other links and lift over

hg19: chr17-7348488;