7-155072129-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024012.4(HTR5A):c.741+489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,986 control chromosomes in the GnomAD database, including 34,292 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 0.67 (34292 hom., cov: 31)
• Consequence: HTR5A NM_024012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

HTR5A (HGNC:5300): (5-hydroxytryptamine receptor 5A) The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. [provided by RefSeq, Jul 2008]

HTR5A-AS1 (HGNC:48956): (HTR5A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR5A	NM_024012.4	c.741+489C>T		intron_variant		ENST00000287907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR5A	ENST00000287907.3	c.741+489C>T		intron_variant		1	NM_024012.4	P1
HTR5A-AS1	ENST00000671665.1	n.322G>A		non_coding_transcript_exon_variant	1/2
HTR5A	ENST00000649716.1	c.215-64C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101705 AN: 151866 Hom.: 34267 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.670 AC: 101775 AN: 151986 Hom.: 34292 Cov.: 31 AF XY: 0.670 AC XY: 49756 AN XY: 74282

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.664

Alfa AF: 0.690 Hom.: 12780

Bravo AF: 0.675

Asia WGS AF: 0.654 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.0
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs2581841; hg19: chr7-154863839;