rs6090387

chr20-63361195-G-Cchr20-63361195-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000744.7(CHRNA4):c.-30C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,453,094 control chromosomes in the GnomAD database, including 407,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.68 (35383 hom., cov: 26)
  • Exomes 𝑓: 0.75 (372235 hom.)
• Consequence: CHRNA4 NM_000744.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

Genes affected

CHRNA4 (HGNC:1958): (cholinergic receptor nicotinic alpha 4 subunit) This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 20-63361195-G-C is Benign according to our data. Variant chr20-63361195-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA4	NM_000744.7	c.-30C>G		5_prime_UTR_variant	1/6	ENST00000370263.9
LOC100130587	NR_110634.1	n.183-623G>C		intron_variant, non_coding_transcript_variant
CHRNA4	NM_001256573.2	c.-489C>G		5_prime_UTR_variant	1/6
CHRNA4	NR_046317.2	n.155C>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA4	ENST00000370263.9	c.-30C>G		5_prime_UTR_variant	1/6	1	NM_000744.7	P1
	ENST00000370257.1	n.183-623G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 101428 AN: 149920 Hom.: 35357 Cov.: 26

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.661

GnomAD3 exomes AF: 0.707 AC: 52306 AN: 73954 Hom.: 18965 AF XY: 0.698 AC XY: 29829 AN XY: 42718

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.772

Gnomad ASJ exome AF: 0.730

Gnomad EAS exome AF: 0.391

Gnomad SAS exome AF: 0.601

Gnomad FIN exome AF: 0.705

Gnomad NFE exome AF: 0.770

Gnomad OTH exome AF: 0.729

GnomAD4 exome AF: 0.751 AC: 979257 AN: 1303076 Hom.: 372235 Cov.: 48 AF XY: 0.748 AC XY: 478862 AN XY: 640390

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.766

Gnomad4 ASJ exome AF: 0.722

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.599

Gnomad4 FIN exome AF: 0.713

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.724

GnomAD4 genome AF: 0.677 AC: 101490 AN: 150018 Hom.: 35383 Cov.: 26 AF XY: 0.674 AC XY: 49337 AN XY: 73218

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.665

Alfa AF: 0.649 Hom.: 2154

Bravo AF: 0.672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	17
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6090387; hg19: chr20-61992547; COSMIC: COSV104427203; COSMIC: COSV104427203;