NM_024012.4:c.741+489C>T

Variant names:

• chr7-155072129-C-T
• rs2581841
• NM_024012.4:c.741+489C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024012.4. 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
	HTR5A	NM_024012.4	MANE Select	c.741+489C>T		intron	N/A	NP_076917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	ENST00000287907.3	TSL:1 MANE Select	c.741+489C>T		intron	N/A	ENSP00000287907.2
	HTR5A-AS1	ENST00000671665.1		n.322G>A		non_coding_transcript_exon	Exon 1 of 2
	HTR5A	ENST00000649716.1		n.214-64C>T		intron	N/A	ENSP00000497222.1

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

African (AFR) AF: 0.604 AC: 25028 AN: 41424

American (AMR) AF: 0.728 AC: 11117 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2521 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4062 AN: 5184

South Asian (SAS) AF: 0.663 AC: 3192 AN: 4818

European-Finnish (FIN) AF: 0.627 AC: 6616 AN: 10554

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47061 AN: 67942

Other (OTH) AF: 0.664 AC: 1402 AN: 2112

Alfa AF: 0.686 Hom.: 19501

Bravo AF: 0.675

Asia WGS AF: 0.654 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.72
PhyloP100		0.078
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2581841; hg19: chr7-154863839;