rs4707338

chr6-87001473-G-C

Variant summary

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

The NM_000865.3(HTR1E):c.-185-13677G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,122 control chromosomes in the GnomAD database, including 3,282 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 (3282 hom., cov: 32)
• Consequence: HTR1E NM_000865.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR1E	NM_000865.3	c.-185-13677G>C		intron_variant		ENST00000305344.7
HTR1E	XM_011535789.3	c.-185-13677G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR1E	ENST00000305344.7	c.-185-13677G>C		intron_variant		1	NM_000865.3	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27812 AN: 152004 Hom.: 3256 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.183 AC: 27869 AN: 152122 Hom.: 3282 Cov.: 32 AF XY: 0.185 AC XY: 13754 AN XY: 74380

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.176

Alfa AF: 0.147 Hom.: 261

Bravo AF: 0.196

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.40
Dann	Benign	0.25

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: rs4707338; hg19: chr6-87711191;