11-113944632-T-G

Position:

• chr11-113944632-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006028.5(HTR3B):​c.967T>G​(p.Leu323Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,614,166 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (18 hom.)
• Consequence: HTR3B NM_006028.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.749

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

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069458187).
• BP6: Variant 11-113944632-T-G is Benign according to our data. Variant chr11-113944632-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 777860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3B	NM_006028.5	c.967T>G	p.Leu323Val	missense_variant	8/9	ENST00000260191.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3B	ENST00000260191.8	c.967T>G	p.Leu323Val	missense_variant	8/9	1	NM_006028.5	P2
HTR3B	ENST00000537778.5	c.934T>G	p.Leu312Val	missense_variant	7/8	1		A2
HTR3B	ENST00000543092.1	c.*15T>G		3_prime_UTR_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.00316 AC: 481 AN: 152176 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00462

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00337 AC: 847 AN: 251450 Hom.: 0 AF XY: 0.00354 AC XY: 481 AN XY: 135898

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.00705

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00464

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00432

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00416 AC: 6085 AN: 1461872 Hom.: 18 Cov.: 31 AF XY: 0.00418 AC XY: 3037 AN XY: 727238

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00335

Gnomad4 ASJ exome AF: 0.00612

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00453

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.00456

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.00316 AC: 481 AN: 152294 Hom.: 2 Cov.: 32 AF XY: 0.00299 AC XY: 223 AN XY: 74466

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00462

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00403 Hom.: 2

Bravo AF: 0.00322

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00623 AC: 24

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.00320 AC: 389

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00513

EpiControl AF: 0.00456

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.093
DANN	Benign	0.68
DEOGEN2	Benign	0.080	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.0069	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.010	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.20
Sift	Benign	0.17	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.046	B;B
Vest4		0.16
MVP		0.43
MPC		0.19
ClinPred		0.012	T
GERP RS		-7.7
Varity_R		0.056
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs78418698; hg19: chr11-113815354;