Variant 5-63961426-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000524.4(HTR1A):c.294G>A(p.Val98Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,613,856 control chromosomes in the GnomAD database, including 2,792 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 0.077 ( 1429 hom., cov: 33)

Exomes 𝑓: 0.0091 ( 1363 hom. )

Consequence

HTR1A
NM_000524.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.208

Variant links:

Genes affected

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 links:

ENSG00000248285 (HGNC:):

ENSG00000248285 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=-0.208 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR1A	NM_000524.4 linkuse as main transcript	c.294G>A	p.Val98Val	synonymous_variant	1/1	ENST00000323865.5	NP_000515.2	P08908Q5ZGX3A8K5W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR1A	ENST00000323865.5 linkuse as main transcript	c.294G>A	p.Val98Val	synonymous_variant	1/1	6	NM_000524.4	ENSP00000316244.4		P08908
ENSG00000248285	ENST00000502882.1 linkuse as main transcript	n.97-3411G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0767

AC:

11677

AN:

152200

Hom.:

1427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.0342

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.0621

GnomAD3 exomes

AF:

0.0222

AC:

5534

AN:

249836

Hom.:

598

AF XY:

0.0168

AC XY:

2277

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.00398

Gnomad EAS exome

AF:

0.0356

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000850

Gnomad OTH exome

AF:

0.00968

GnomAD4 exome

AF:

0.00911

AC:

13311

AN:

1461536

Hom.:

1363

Cov.:

AF XY:

0.00815

AC XY:

5928

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.274

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.00364

Gnomad4 EAS exome

AF:

0.0366

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000503

Gnomad4 OTH exome

AF:

0.0198

GnomAD4 genome

AF:

0.0768

AC:

11698

AN:

152320

Hom.:

1429

Cov.:

AF XY:

0.0743

AC XY:

5535

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.0341

Gnomad4 SAS

AF:

0.00434

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.0614

Alfa

AF:

0.0212

Hom.:

433

Bravo

AF:

0.0895

Asia WGS

AF:

0.0300

AC:

103

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000892

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.6

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over