1-23210398-C-G

Position:

• chr1-23210398-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000864.5(HTR1D):​c.-783+6893G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,052 control chromosomes in the GnomAD database, including 19,187 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 0.49 (19187 hom., cov: 32)
• Consequence: HTR1D NM_000864.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR1D	NM_000864.5	c.-783+6893G>C		intron_variant		ENST00000374619.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR1D	ENST00000374619.2	c.-783+6893G>C		intron_variant			NM_000864.5	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74771 AN: 151934 Hom.: 19136 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.492 AC: 74884 AN: 152052 Hom.: 19187 Cov.: 32 AF XY: 0.493 AC XY: 36633 AN XY: 74318

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.495

Alfa AF: 0.428 Hom.: 8034

Bravo AF: 0.506

Asia WGS AF: 0.555 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1738475; hg19: chr1-23536891; COSMIC: COSV59931537;