rs4707338

Variant names:

• chr6-87001473-G-C
• rs4707338
• NM_000865.3:c.-185-13677G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000301944 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HTR1E	NM_000865.3	c.-185-13677G>C		intron_variant	Intron 1 of 1	ENST00000305344.7	NP_000856.1
HTR1E	XM_011535789.3	c.-185-13677G>C		intron_variant	Intron 1 of 1		XP_011534091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1E	ENST00000305344.7	c.-185-13677G>C		intron_variant	Intron 1 of 1	1	NM_000865.3	ENSP00000307766.4
ENSG00000301944	ENST00000783020.1	n.145+8987C>G		intron_variant	Intron 1 of 2
ENSG00000301944	ENST00000783021.1	n.152+8987C>G		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.323 AC: 13401 AN: 41466

American (AMR) AF: 0.179 AC: 2741 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1597 AN: 5164

South Asian (SAS) AF: 0.152 AC: 735 AN: 4828

European-Finnish (FIN) AF: 0.0970 AC: 1027 AN: 10592

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7238 AN: 67996

Other (OTH) AF: 0.176 AC: 371 AN: 2112

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
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4707338; hg19: chr6-87711191;