rs856510

Variant names:

• chr1-23197914-A-C
• rs856510
• NM_000864.5:c.-782-2913T>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.-782-2913T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,576 control chromosomes in the GnomAD database, including 9,852 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 0.35 (9852 hom., cov: 29)
• Consequence: HTR1D NM_000864.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 7 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 = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1D	NM_000864.5	c.-782-2913T>G		intron_variant	Intron 1 of 1	ENST00000374619.2	NP_000855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1D	ENST00000374619.2	c.-782-2913T>G		intron_variant	Intron 1 of 1	6	NM_000864.5	ENSP00000363748.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53147 AN: 151458 Hom.: 9826 Cov.: 29

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.351 AC: 53229 AN: 151576 Hom.: 9852 Cov.: 29 AF XY: 0.348 AC XY: 25799 AN XY: 74062

African (AFR) AF: 0.471 AC: 19450 AN: 41286

American (AMR) AF: 0.281 AC: 4276 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1380 AN: 5142

South Asian (SAS) AF: 0.269 AC: 1289 AN: 4784

European-Finnish (FIN) AF: 0.327 AC: 3424 AN: 10458

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21096 AN: 67894

Other (OTH) AF: 0.342 AC: 721 AN: 2106

Alfa AF: 0.330 Hom.: 1121

Bravo AF: 0.354

Asia WGS AF: 0.279 AC: 970 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	1.1
DANN	Benign	0.49
PhyloP100		-0.71

Splicing

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

Other links and lift over

dbSNP: rs856510; hg19: chr1-23524407; COSMIC: COSV58447675;