rs856510

Positions:

• chr1-23197914-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HTR1D	NM_000864.5	c.-782-2913T>G		intron_variant		ENST00000374619.2	NP_000855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR1D	ENST00000374619.2	c.-782-2913T>G		intron_variant		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

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.342

Alfa AF: 0.324 Hom.: 1029

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

Splicing

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

Publications

LitVar

Other links and lift over

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