chr1-23195342-G-A

Position:

• chr1-23195342-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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.-782-341C>T		intron_variant		ENST00000374619.2	NP_000855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR1D	ENST00000374619.2	c.-782-341C>T		intron_variant			NM_000864.5	ENSP00000363748	P1

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

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.342

Alfa AF: 0.233 Hom.: 678

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	-0.85
CADD	Benign	4.2
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

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