rs6474414

Variant names:

• chr8-42705193-A-C
• rs6474414
• NM_000749.5:c.53-3524A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-42705193-A-C
• chr8-42705193-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000749.5(CHRNB3):​c.53-3524A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,102 control chromosomes in the GnomAD database, including 33,226 homozygotes. 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: 𝑓 0.61 (33226 hom., cov: 32)
• Consequence: CHRNB3 NM_000749.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 11 publications found

Genes affected

CHRNB3 (HGNC:1963): (cholinergic receptor nicotinic beta 3 subunit) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are (hetero)pentamers composed of homologous subunits. The subunits that make up the muscle and neuronal forms of nAChRs are encoded by separate genes and have different primary structure. There are several subtypes of neuronal nAChRs that vary based on which homologous subunits are arranged around the central channel. They are classified as alpha-subunits if, like muscle alpha-1 (MIM 100690), they have a pair of adjacent cysteines as part of the presumed acetylcholine binding site. Subunits lacking these cysteine residues are classified as beta-subunits (Groot Kormelink and Luyten, 1997 [PubMed 9009220]). Elliott et al. (1996) [PubMed 8906617] stated that the proposed structure for each subunit is a conserved N-terminal extracellular domain followed by 3 conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region.[supplied by OMIM, Apr 2010]

LOC105379396 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB3	NM_000749.5	c.53-3524A>C		intron_variant	Intron 1 of 5	ENST00000289957.3	NP_000740.1
LOC105379396	XR_007060900.1	n.983T>G		non_coding_transcript_exon_variant	Exon 2 of 2
CHRNB3	NM_001347717.2	c.-171+712A>C		intron_variant	Intron 2 of 6		NP_001334646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB3	ENST00000289957.3	c.53-3524A>C		intron_variant	Intron 1 of 5	1	NM_000749.5	ENSP00000289957.2
CHRNB3	ENST00000534391.1	c.-171+712A>C		intron_variant	Intron 2 of 3	3		ENSP00000433913.1
CHRNB3	ENST00000531610.5	n.472+712A>C		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93368 AN: 151984 Hom.: 33219 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.614 AC: 93388 AN: 152102 Hom.: 33226 Cov.: 32 AF XY: 0.620 AC XY: 46081 AN XY: 74338

African (AFR) AF: 0.227 AC: 9413 AN: 41494

American (AMR) AF: 0.705 AC: 10778 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2424 AN: 3464

East Asian (EAS) AF: 0.807 AC: 4160 AN: 5158

South Asian (SAS) AF: 0.706 AC: 3403 AN: 4818

European-Finnish (FIN) AF: 0.759 AC: 8031 AN: 10576

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.777 AC: 52863 AN: 67992

Other (OTH) AF: 0.647 AC: 1368 AN: 2114

Alfa AF: 0.728 Hom.: 19359

Bravo AF: 0.592

Asia WGS AF: 0.701 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.46
DANN	Benign	0.57
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs6474414; hg19: chr8-42560336;