chr15-78580878-C-T

Variant names:

• chr15-78580878-C-T
• rs79835149
• NM_000745.4:c.174C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000745.4(CHRNA5):​c.174C>T​(p.Tyr58Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,613,482 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (56 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (62 hom.)
• Consequence: CHRNA5 NM_000745.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.416
• Publications: 6 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 15-78580878-C-T is Benign according to our data. Variant chr15-78580878-C-T is described in ClinVar as Benign. ClinVar VariationId is 714660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.416 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

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.174C>T	p.Tyr58Tyr	synonymous	Exon 2 of 6	NP_000736.2
	CHRNA5	NM_001395171.1		c.174C>T	p.Tyr58Tyr	synonymous	Exon 2 of 6	NP_001382100.1
	CHRNA5	NM_001395172.1		c.174C>T	p.Tyr58Tyr	synonymous	Exon 2 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.174C>T	p.Tyr58Tyr	synonymous	Exon 2 of 6	ENSP00000299565.5	P30532
	CHRNA5	ENST00000913028.1		c.174C>T	p.Tyr58Tyr	synonymous	Exon 2 of 6	ENSP00000583087.1
	CHRNA5	ENST00000559554.5	TSL:3	c.174C>T	p.Tyr58Tyr	synonymous	Exon 2 of 6	ENSP00000453519.1	H0YM98

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2411 AN: 152184 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00520

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00418 AC: 1052 AN: 251408 AF XY: 0.00301

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00175 AC: 2555 AN: 1461180 Hom.: 62 Cov.: 30 AF XY: 0.00154 AC XY: 1118 AN XY: 726964

African (AFR) AF: 0.0565 AC: 1889 AN: 33460

American (AMR) AF: 0.00268 AC: 120 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00555 AC: 145 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86236

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5766

European-Non Finnish (NFE) AF: 0.000130 AC: 144 AN: 1111414

Other (OTH) AF: 0.00373 AC: 225 AN: 60362

GnomAD4 genome AF: 0.0159 AC: 2422 AN: 152302 Hom.: 56 Cov.: 33 AF XY: 0.0152 AC XY: 1132 AN XY: 74480

African (AFR) AF: 0.0548 AC: 2280 AN: 41568

American (AMR) AF: 0.00497 AC: 76 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00520 AC: 18 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68016

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.0425 Hom.: 2384

Bravo AF: 0.0177

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	4.7
DANN	Benign	0.60
PhyloP100		-0.42
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism

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: rs79835149; hg19: chr15-78873220; COSMIC: COSV107346676; COSMIC: COSV107346676;