NM_006028.5:c.696+72A>G

Variant names:

• chr11-113933165-A-G
• rs2276307
• NM_006028.5:c.696+72A>G

Variant summary

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

The NM_006028.5(HTR3B):​c.696+72A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,460,512 control chromosomes in the GnomAD database, including 38,659 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 0.20 (3250 hom., cov: 32)
  • Exomes 𝑓: 0.23 (35409 hom.)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 30 publications found

Genes affected

HTR3B (HGNC:5298): (5-hydroxytryptamine receptor 3B) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit B of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. It is not functional as a homomeric complex, but a pentaheteromeric complex with subunit A (HTR3A) displays the full functional features of this receptor. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.696+72A>G		intron_variant	Intron 6 of 8	ENST00000260191.8	NP_006019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3B	ENST00000260191.8	c.696+72A>G		intron_variant	Intron 6 of 8	1	NM_006028.5	ENSP00000260191.2
HTR3B	ENST00000537778.5	c.663+72A>G		intron_variant	Intron 5 of 7	1		ENSP00000443118.1
HTR3B	ENST00000543092.1	c.480+72A>G		intron_variant	Intron 4 of 4	3		ENSP00000440894.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30123 AN: 152000 Hom.: 3240 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.230 AC: 301235 AN: 1308394 Hom.: 35409 AF XY: 0.234 AC XY: 151564 AN XY: 648982

African (AFR) AF: 0.110 AC: 3224 AN: 29376

American (AMR) AF: 0.240 AC: 8524 AN: 35478

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 6430 AN: 22004

East Asian (EAS) AF: 0.227 AC: 8666 AN: 38256

South Asian (SAS) AF: 0.330 AC: 24110 AN: 72974

European-Finnish (FIN) AF: 0.179 AC: 8947 AN: 49924

Middle Eastern (MID) AF: 0.260 AC: 1095 AN: 4214

European-Non Finnish (NFE) AF: 0.227 AC: 227662 AN: 1001810

Other (OTH) AF: 0.231 AC: 12577 AN: 54358

GnomAD4 genome AF: 0.198 AC: 30139 AN: 152118 Hom.: 3250 Cov.: 32 AF XY: 0.198 AC XY: 14689 AN XY: 74364

African (AFR) AF: 0.121 AC: 5021 AN: 41502

American (AMR) AF: 0.223 AC: 3402 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1005 AN: 3472

East Asian (EAS) AF: 0.172 AC: 889 AN: 5174

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4830

European-Finnish (FIN) AF: 0.179 AC: 1897 AN: 10590

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.230 AC: 15612 AN: 67988

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.217 Hom.: 7902

Bravo AF: 0.194

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.34
PhyloP100		-0.48
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: rs2276307; hg19: chr11-113803887; COSMIC: COSV52747587;