6-86942024-C-T

Variant names:

• chr6-86942024-C-T
• rs10944288
• NM_000865.3:c.-186+4201C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000865.3(HTR1E):​c.-186+4201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,994 control chromosomes in the GnomAD database, including 31,571 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 0.64 (31571 hom., cov: 32)
• Consequence: HTR1E NM_000865.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 18 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000865.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1E	NM_000865.3	MANE Select	c.-186+4201C>T		intron	N/A	NP_000856.1	P28566

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1E	ENST00000305344.7	TSL:1 MANE Select	c.-186+4201C>T		intron	N/A	ENSP00000307766.4	P28566
	HTR1E	ENST00000962028.1		c.-186+4201C>T		intron	N/A	ENSP00000632087.1
	HTR1E	ENST00000962029.1		c.-186+4140C>T		intron	N/A	ENSP00000632088.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97702 AN: 151876 Hom.: 31536 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.643 AC: 97785 AN: 151994 Hom.: 31571 Cov.: 32 AF XY: 0.645 AC XY: 47945 AN XY: 74288

African (AFR) AF: 0.590 AC: 24466 AN: 41434

American (AMR) AF: 0.715 AC: 10928 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2487 AN: 3466

East Asian (EAS) AF: 0.574 AC: 2956 AN: 5152

South Asian (SAS) AF: 0.633 AC: 3053 AN: 4820

European-Finnish (FIN) AF: 0.659 AC: 6959 AN: 10562

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.658 AC: 44733 AN: 67960

Other (OTH) AF: 0.640 AC: 1351 AN: 2110

Alfa AF: 0.654 Hom.: 74763

Bravo AF: 0.643

Asia WGS AF: 0.590 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		0.11
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: rs10944288; hg19: chr6-87651742;