rs961390206

Variant names:

• chr15-78565806-G-A
• rs961390206
• NM_000745.4:c.87G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000745.4(CHRNA5):​c.87G>A​(p.Ala29Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRNA5 NM_000745.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.143
• Publications: 0 publications found

Genes affected

CHRNA5 (HGNC:1959): (cholinergic receptor nicotinic alpha 5 subunit) The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 15-78565806-G-A is Benign according to our data. Variant chr15-78565806-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 741134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.143 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000745.4. 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
	CHRNA5	NM_000745.4	MANE Select	c.87G>A	p.Ala29Ala	synonymous	Exon 1 of 6	NP_000736.2
	CHRNA5	NM_001395171.1		c.87G>A	p.Ala29Ala	synonymous	Exon 1 of 6	NP_001382100.1
	CHRNA5	NM_001395172.1		c.87G>A	p.Ala29Ala	synonymous	Exon 1 of 6	NP_001382101.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.87G>A	p.Ala29Ala	synonymous	Exon 1 of 6	ENSP00000299565.5	P30532
	CHRNA5	ENST00000913028.1		c.87G>A	p.Ala29Ala	synonymous	Exon 1 of 6	ENSP00000583087.1
	CHRNA5	ENST00000559554.5	TSL:3	c.87G>A	p.Ala29Ala	synonymous	Exon 1 of 6	ENSP00000453519.1	H0YM98

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1071136 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 505824

African (AFR) AF: 0.00 AC: 0 AN: 22516

American (AMR) AF: 0.00 AC: 0 AN: 8118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13940

East Asian (EAS) AF: 0.00 AC: 0 AN: 26024

South Asian (SAS) AF: 0.00 AC: 0 AN: 19416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2880

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 914356

Other (OTH) AF: 0.00 AC: 0 AN: 42992

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.5
DANN	Benign	0.96
PhyloP100		-0.14
PromoterAI		-0.0057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

Other links and lift over

dbSNP: rs961390206; hg19: chr15-78858148;