7-155082904-C-T

Variant names:

• chr7-155082904-C-T
• rs1657268
• NM_024012.4:c.742-1251C>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.742-1251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,000 control chromosomes in the GnomAD database, including 23,455 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 0.54 (23455 hom., cov: 32)
• Consequence: HTR5A NM_024012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 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.742-1251C>T		intron	N/A	NP_076917.1	A4D2N2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	ENST00000287907.3	TSL:1 MANE Select	c.742-1251C>T		intron	N/A	ENSP00000287907.2	P47898
	HTR5A	ENST00000486819.1	TSL:1	n.98-1251C>T		intron	N/A
	HTR5A	ENST00000649716.1		n.*211-1251C>T		intron	N/A	ENSP00000497222.1	A0A3B3ISH0

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81891 AN: 151882 Hom.: 23452 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.539 AC: 81914 AN: 152000 Hom.: 23455 Cov.: 32 AF XY: 0.541 AC XY: 40187 AN XY: 74284

African (AFR) AF: 0.322 AC: 13324 AN: 41416

American (AMR) AF: 0.598 AC: 9145 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2191 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3175 AN: 5166

South Asian (SAS) AF: 0.618 AC: 2981 AN: 4824

European-Finnish (FIN) AF: 0.568 AC: 5998 AN: 10566

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.637 AC: 43263 AN: 67958

Other (OTH) AF: 0.553 AC: 1167 AN: 2112

Alfa AF: 0.565 Hom.: 4327

Bravo AF: 0.529

Asia WGS AF: 0.561 AC: 1950 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.17
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1657268; hg19: chr7-154874614;