rs1042500

Variant names:

• chr15-78590605-G-C
• rs1042500
• NM_000745.4:c.1214G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000745.4(CHRNA5):​c.1214G>C​(p.Arg405Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHRNA5 NM_000745.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.27
• 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]

ENSG00000261762 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37825632).

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.1214G>C	p.Arg405Thr	missense	Exon 5 of 6	NP_000736.2
	CHRNA5	NM_001395171.1		c.1115+99G>C		intron	N/A	NP_001382100.1
	CHRNA5	NM_001395172.1		c.591+623G>C		intron	N/A	NP_001382101.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.1214G>C	p.Arg405Thr	missense	Exon 5 of 6	ENSP00000299565.5	P30532
	CHRNA5	ENST00000913028.1		c.591+623G>C		intron	N/A	ENSP00000583087.1
	CHRNA5	ENST00000394802.4	TSL:3	c.521+507G>C		intron	N/A	ENSP00000378281.4	H7BYM0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.35
Sift	Benign	0.062	T
Sift4G	Uncertain	0.056	T
Polyphen		0.38	B
Vest4		0.37
MutPred		0.62		Loss of MoRF binding (P = 0.0141)
MVP		0.75
MPC		0.43
ClinPred		0.86	D
GERP RS		4.8
PromoterAI		0.0033	Neutral
Varity_R		0.24
gMVP		0.49

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: rs1042500; hg19: chr15-78882947;