rs3734119

Variant names:

• chr5-148510060-A-G
• rs3734119
• NM_000870.7:c.508-36T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-148510060-A-G
• chr5-148510060-A-T

Variant summary

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

The NM_001040173.2(HTR4):​c.508-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,400,284 control chromosomes in the GnomAD database, including 9,018 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 0.15 (3322 hom., cov: 31)
  • Exomes 𝑓: 0.066 (5696 hom.)
• Consequence: HTR4 NM_001040173.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 2 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]

ENSG00000300418 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040173.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	NM_000870.7	MANE Select	c.508-36T>C		intron	N/A	NP_000861.1
	HTR4	NM_001040173.2		c.508-36T>C		intron	N/A	NP_001035263.1
	HTR4	NM_001286410.1		c.508-36T>C		intron	N/A	NP_001273339.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000377888.8	TSL:1 MANE Select	c.508-36T>C		intron	N/A	ENSP00000367120.4
	HTR4	ENST00000520514.5	TSL:1	c.508-36T>C		intron	N/A	ENSP00000427913.1
	HTR4	ENST00000521530.6	TSL:1	c.508-36T>C		intron	N/A	ENSP00000428320.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23493 AN: 151686 Hom.: 3321 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0769

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.122 AC: 20658 AN: 169514 AF XY: 0.111

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.0466

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.0719

Gnomad NFE exome AF: 0.0499

Gnomad OTH exome AF: 0.0903

GnomAD4 exome AF: 0.0660 AC: 82419 AN: 1248480 Hom.: 5696 Cov.: 16 AF XY: 0.0646 AC XY: 40072 AN XY: 620762

African (AFR) AF: 0.370 AC: 10408 AN: 28110

American (AMR) AF: 0.195 AC: 6190 AN: 31792

Ashkenazi Jewish (ASJ) AF: 0.0407 AC: 873 AN: 21454

East Asian (EAS) AF: 0.287 AC: 10686 AN: 37278

South Asian (SAS) AF: 0.0733 AC: 5198 AN: 70932

European-Finnish (FIN) AF: 0.0706 AC: 3565 AN: 50518

Middle Eastern (MID) AF: 0.0333 AC: 173 AN: 5196

European-Non Finnish (NFE) AF: 0.0431 AC: 40927 AN: 950666

Other (OTH) AF: 0.0837 AC: 4399 AN: 52534

GnomAD4 genome AF: 0.155 AC: 23516 AN: 151804 Hom.: 3322 Cov.: 31 AF XY: 0.155 AC XY: 11495 AN XY: 74204

African (AFR) AF: 0.366 AC: 15118 AN: 41292

American (AMR) AF: 0.159 AC: 2426 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 130 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1445 AN: 5158

South Asian (SAS) AF: 0.0765 AC: 366 AN: 4782

European-Finnish (FIN) AF: 0.0644 AC: 682 AN: 10588

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0445 AC: 3025 AN: 67946

Other (OTH) AF: 0.129 AC: 272 AN: 2110

Alfa AF: 0.0956 Hom.: 320

Bravo AF: 0.171

Asia WGS AF: 0.162 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.64
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3734119; hg19: chr5-147889623; COSMIC: COSV58790879;