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. The variant received -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
• Publications: 394 publications found

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]

HTR1A Gene-Disease associations (from GenCC):

• menstrual cycle-dependent periodic fever

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502882.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000248285	ENST00000502882.1	TSL:2	n.97-4723G>C		intron	N/A
	HTR1A	ENST00000506598.1	TSL:4	c.-659G>C		upstream_gene	N/A	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

African (AFR) AF: 0.440 AC: 18241 AN: 41428

American (AMR) AF: 0.488 AC: 7461 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3468

East Asian (EAS) AF: 0.757 AC: 3899 AN: 5150

South Asian (SAS) AF: 0.585 AC: 2816 AN: 4812

European-Finnish (FIN) AF: 0.426 AC: 4505 AN: 10578

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33999 AN: 67960

Other (OTH) AF: 0.506 AC: 1066 AN: 2106

Alfa AF: 0.479 Hom.: 2152

Bravo AF: 0.491

Asia WGS AF: 0.634 AC: 2206 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.69
PhyloP100		-0.72
PromoterAI		-0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6295; hg19: chr5-63258565;