rs1406946

Positions:

• chr6-86937873-C-T

Variant summary

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

The NM_000865.3(HTR1E):​c.-186+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,710 control chromosomes in the GnomAD database, including 11,555 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 0.36 (11496 hom., cov: 32)
  • Exomes 𝑓: 0.46 (59 hom.)
• Consequence: HTR1E NM_000865.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776

Genes affected

HTR1E (HGNC:5291): (5-hydroxytryptamine receptor 1E) Enables G protein-coupled serotonin receptor activity and serotonin binding activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway. 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR1E	NM_000865.3	c.-186+50C>T		intron_variant		ENST00000305344.7	NP_000856.1
HTR1E	XM_011535789.3	c.-197C>T		5_prime_UTR_variant	1/2		XP_011534091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR1E	ENST00000305344.7	c.-186+50C>T		intron_variant		1	NM_000865.3	ENSP00000307766	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54474 AN: 152008 Hom.: 11496 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.455 AC: 266 AN: 584 Hom.: 59 Cov.: 0 AF XY: 0.475 AC XY: 168 AN XY: 354

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.358 AC: 54475 AN: 152126 Hom.: 11496 Cov.: 32 AF XY: 0.358 AC XY: 26645 AN XY: 74368

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.342

Alfa AF: 0.423 Hom.: 3404

Bravo AF: 0.338

Asia WGS AF: 0.324 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1406946; hg19: chr6-87647591; COSMIC: COSV59509241;