rs6597455

Variant names:

• chr7-155079655-C-G
• rs6597455
• NM_024012.4:c.742-4500C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024012.4(HTR5A):​c.742-4500C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,004 control chromosomes in the GnomAD database, including 8,693 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 0.34 (8693 hom., cov: 32)
• Consequence: HTR5A NM_024012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4	c.742-4500C>G		intron_variant	Intron 1 of 1	ENST00000287907.3	NP_076917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR5A	ENST00000287907.3	c.742-4500C>G		intron_variant	Intron 1 of 1	1	NM_024012.4	ENSP00000287907.2
HTR5A	ENST00000486819.1	n.97+2421C>G		intron_variant	Intron 1 of 1	1
HTR5A	ENST00000649716.1	n.*211-4500C>G		intron_variant	Intron 2 of 2			ENSP00000497222.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51003 AN: 151886 Hom.: 8676 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.336 AC: 51057 AN: 152004 Hom.: 8693 Cov.: 32 AF XY: 0.338 AC XY: 25128 AN XY: 74290

African (AFR) AF: 0.321 AC: 13318 AN: 41452

American (AMR) AF: 0.318 AC: 4853 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1077 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1966 AN: 5180

South Asian (SAS) AF: 0.335 AC: 1615 AN: 4824

European-Finnish (FIN) AF: 0.411 AC: 4333 AN: 10532

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22762 AN: 67974

Other (OTH) AF: 0.331 AC: 697 AN: 2104

Alfa AF: 0.342 Hom.: 1142

Bravo AF: 0.329

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.35
PhyloP100		-0.31
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: rs6597455; hg19: chr7-154871365;