chr1-23194847-G-A

Position:

• chr1-23194847-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.-628C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,544 control chromosomes in the GnomAD database, including 2,499 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 0.18 (2495 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4 hom.)
• Consequence: HTR1D NM_000864.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR1D	NM_000864.5	c.-628C>T		5_prime_UTR_variant	2/2	ENST00000374619.2	NP_000855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR1D	ENST00000374619.2	c.-628C>T		5_prime_UTR_variant	2/2		NM_000864.5	ENSP00000363748	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27047 AN: 151934 Hom.: 2490 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.144 AC: 71 AN: 492 Hom.: 4 AF XY: 0.156 AC XY: 45 AN XY: 288

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.178 AC: 27069 AN: 152052 Hom.: 2495 Cov.: 32 AF XY: 0.177 AC XY: 13167 AN XY: 74332

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.173

Alfa AF: 0.171 Hom.: 583

Bravo AF: 0.182

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.4
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs676643; hg19: chr1-23521340;