rs674386

Variant names:

• chr1-23195342-G-A
• rs674386
• NM_000864.5:c.-782-341C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-23195342-G-A
• chr1-23195342-G-T

Variant summary

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

The NM_000864.5(HTR1D):​c.-782-341C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,000 control chromosomes in the GnomAD database, including 9,910 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 (9910 hom., cov: 32)
• Consequence: HTR1D NM_000864.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840
• Publications: 14 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000864.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1D	NM_000864.5	MANE Select	c.-782-341C>T		intron	N/A	NP_000855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1D	ENST00000374619.2	TSL:6 MANE Select	c.-782-341C>T		intron	N/A	ENSP00000363748.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53362 AN: 151888 Hom.: 9884 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.408

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: 0.352 AC: 53444 AN: 152000 Hom.: 9910 Cov.: 32 AF XY: 0.349 AC XY: 25921 AN XY: 74328

African (AFR) AF: 0.472 AC: 19541 AN: 41422

American (AMR) AF: 0.281 AC: 4296 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1387 AN: 5174

South Asian (SAS) AF: 0.271 AC: 1309 AN: 4822

European-Finnish (FIN) AF: 0.327 AC: 3445 AN: 10546

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.311 AC: 21150 AN: 67968

Other (OTH) AF: 0.342 AC: 723 AN: 2112

Alfa AF: 0.291 Hom.: 2148

Bravo AF: 0.354

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.65
PhyloP100		0.84

Splicing

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

Other links and lift over

dbSNP: rs674386; hg19: chr1-23521835; COSMIC: COSV58447627;