ENST00000502882.1:n.97-4723G>C

Variant names:

• chr5-63962738-C-G
• rs6295
• ENST00000502882.1:n.97-4723G>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000502882.1(ENSG00000248285):​n.97-4723G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,978 control chromosomes in the GnomAD database, including 18,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.49 (18681 hom., cov: 32)
• Consequence: ENSG00000248285 ENST00000502882.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.716

Genes affected

ENSG00000248285 (HGNC:):

HTR1A (HGNC:5286): (5-hydroxytryptamine receptor 1A) This gene encodes a G protein-coupled receptor for 5-hydroxytryptamine (serotonin), and belongs to the 5-hydroxytryptamine receptor subfamily. Serotonin has been implicated in a number of physiologic processes and pathologic conditions. Inactivation of this gene in mice results in behavior consistent with an increased anxiety and stress response. Mutation in the promoter of this gene has been associated with menstrual cycle-dependent periodic fevers. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-63962738-C-G is Benign according to our data. Variant chr5-63962738-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 375667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000248285	ENST00000502882.1	n.97-4723G>C		intron_variant	Intron 1 of 1	2
HTR1A	ENST00000506598.1	c.-659G>C		upstream_gene_variant		4		ENSP00000423433.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74590 AN: 151860 Hom.: 18657 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.491 AC: 74651 AN: 151978 Hom.: 18681 Cov.: 32 AF XY: 0.491 AC XY: 36500 AN XY: 74302

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.506

Alfa AF: 0.479 Hom.: 2152

Bravo AF: 0.491

Asia WGS AF: 0.634 AC: 2206 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6295; hg19: chr5-63258565;