rs604030

Variant names:

• chr1-23191734-T-C
• rs604030
• NM_000864.5:c.*1352A>G

Variant summary

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

The NM_000864.5(HTR1D):​c.*1352A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,888 control chromosomes in the GnomAD database, including 11,202 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 0.38 (11202 hom., cov: 31)
• Consequence: HTR1D NM_000864.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 8 publications found

Genes affected

HTR1D (HGNC:5289): (5-hydroxytryptamine receptor 1D) Enables G protein-coupled serotonin receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and intestine smooth muscle contraction. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1D	NM_000864.5	c.*1352A>G		downstream_gene_variant		ENST00000374619.2	NP_000855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1D	ENST00000374619.2	c.*1352A>G		downstream_gene_variant		6	NM_000864.5	ENSP00000363748.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57088 AN: 151770 Hom.: 11176 Cov.: 31

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.376 AC: 57172 AN: 151888 Hom.: 11202 Cov.: 31 AF XY: 0.373 AC XY: 27682 AN XY: 74250

African (AFR) AF: 0.480 AC: 19880 AN: 41404

American (AMR) AF: 0.314 AC: 4788 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1392 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1385 AN: 5156

South Asian (SAS) AF: 0.274 AC: 1316 AN: 4808

European-Finnish (FIN) AF: 0.349 AC: 3682 AN: 10552

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23536 AN: 67952

Other (OTH) AF: 0.377 AC: 793 AN: 2104

Alfa AF: 0.373 Hom.: 1635

Bravo AF: 0.380

Asia WGS AF: 0.281 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.47
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs604030; hg19: chr1-23518227; COSMIC: COSV58447619;