rs6300

Positions:

• chr1-23193140-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000864.5(HTR1D):​c.1080T>C​(p.Asn360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,054 control chromosomes in the GnomAD database, including 16,786 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 0.14 (1917 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14869 hom.)
• Consequence: HTR1D NM_000864.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.508 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR1D	NM_000864.5	c.1080T>C	p.Asn360=	synonymous_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.1080T>C	p.Asn360=	synonymous_variant	2/2		NM_000864.5	ENSP00000363748	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21721 AN: 151940 Hom.: 1917 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.147

GnomAD3 exomes AF: 0.165 AC: 41331 AN: 250662 Hom.: 4787 AF XY: 0.163 AC XY: 22132 AN XY: 135470

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.0966

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.317

Gnomad FIN exome AF: 0.0738

Gnomad NFE exome AF: 0.0990

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.125 AC: 182797 AN: 1460996 Hom.: 14869 Cov.: 33 AF XY: 0.129 AC XY: 94018 AN XY: 726748

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.0952

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.0689

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.143 AC: 21751 AN: 152058 Hom.: 1917 Cov.: 32 AF XY: 0.147 AC XY: 10900 AN XY: 74342

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.153

Alfa AF: 0.113 Hom.: 561

Bravo AF: 0.155

Asia WGS AF: 0.274 AC: 951 AN: 3478

EpiCase AF: 0.0978

EpiControl AF: 0.0981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.40
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6300; hg19: chr1-23519633; COSMIC: COSV58448110;