1-23193662-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000864.5(HTR1D):c.558G>A(p.Ser186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,613,264 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (25 hom.)
• Consequence: HTR1D NM_000864.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.76

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-23193662-C-T is Benign according to our data. Variant chr1-23193662-C-T is described in ClinVar as [Benign]. Clinvar id is 773393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.76 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR1D	NM_000864.5	c.558G>A	p.Ser186=	synonymous_variant	2/2	ENST00000374619.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR1D	ENST00000374619.2	c.558G>A	p.Ser186=	synonymous_variant	2/2		NM_000864.5	P1

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 593 AN: 152208 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00573

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00386 AC: 966 AN: 249978 Hom.: 3 AF XY: 0.00405 AC XY: 547 AN XY: 135066

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000724

Gnomad ASJ exome AF: 0.00383

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00128

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.00525

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00485 AC: 7090 AN: 1460938 Hom.: 25 Cov.: 33 AF XY: 0.00479 AC XY: 3479 AN XY: 726674

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000806

Gnomad4 ASJ exome AF: 0.00384

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00183

Gnomad4 FIN exome AF: 0.0131

Gnomad4 NFE exome AF: 0.00524

Gnomad4 OTH exome AF: 0.00423

GnomAD4 genome AF: 0.00389 AC: 593 AN: 152326 Hom.: 4 Cov.: 32 AF XY: 0.00393 AC XY: 293 AN XY: 74486

Gnomad4 AFR AF: 0.000625

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.00573

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00442 Hom.: 2

Bravo AF: 0.00261

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00409

EpiControl AF: 0.00433

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.34
Dann	Benign	0.51

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: rs143458420; hg19: chr1-23520155;