NM_000870.7:c.27-29361A>G

Variant names:

• chr5-148579623-T-C
• rs4336354
• NM_000870.7:c.27-29361A>G

Variant summary

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

The NM_000870.7(HTR4):​c.27-29361A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,996 control chromosomes in the GnomAD database, including 5,376 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 0.24 (5376 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 3 publications found

Genes affected

HTR4 (HGNC:5299): (5-hydroxytryptamine receptor 4) This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described. [provided by RefSeq, May 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7	c.27-29361A>G		intron_variant	Intron 2 of 6	ENST00000377888.8	NP_000861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.27-29361A>G		intron_variant	Intron 2 of 6	1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36642 AN: 151878 Hom.: 5372 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.241 AC: 36643 AN: 151996 Hom.: 5376 Cov.: 32 AF XY: 0.237 AC XY: 17596 AN XY: 74282

African (AFR) AF: 0.0785 AC: 3260 AN: 41538

American (AMR) AF: 0.268 AC: 4089 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1241 AN: 5138

South Asian (SAS) AF: 0.214 AC: 1033 AN: 4820

European-Finnish (FIN) AF: 0.258 AC: 2731 AN: 10572

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22710 AN: 67910

Other (OTH) AF: 0.240 AC: 506 AN: 2108

Alfa AF: 0.306 Hom.: 3891

Bravo AF: 0.238

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.0
DANN	Benign	0.79
PhyloP100		0.32
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: rs4336354; hg19: chr5-147959186; COSMIC: COSV58792000;