chr7-155070724-T-C

Variant names:

• chr7-155070724-T-C
• rs3734966
• NM_024012.4:c.-176T>C

Variant summary

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

The NM_024012.4(HTR5A):​c.-176T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 687,090 control chromosomes in the GnomAD database, including 4,970 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 0.14 (1962 hom., cov: 33)
  • Exomes 𝑓: 0.095 (3008 hom.)
• Consequence: HTR5A NM_024012.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• 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]

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	NM_024012.4	MANE Select	c.-176T>C		5_prime_UTR	Exon 1 of 2	NP_076917.1
	HTR5A-AS1	NR_038945.1		n.524+310A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	ENST00000287907.3	TSL:1 MANE Select	c.-176T>C		5_prime_UTR	Exon 1 of 2	ENSP00000287907.2
	HTR5A-AS1	ENST00000395731.5	TSL:1	n.524+310A>G		intron	N/A
	HTR5A-AS1	ENST00000493904.3	TSL:4	n.551+310A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21125 AN: 151922 Hom.: 1957 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0951 AC: 50871 AN: 535050 Hom.: 3008 Cov.: 6 AF XY: 0.0937 AC XY: 26299 AN XY: 280678

African (AFR) AF: 0.264 AC: 3880 AN: 14716

American (AMR) AF: 0.193 AC: 4189 AN: 21662

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 1954 AN: 14236

East Asian (EAS) AF: 0.150 AC: 5034 AN: 33610

South Asian (SAS) AF: 0.0946 AC: 4695 AN: 49612

European-Finnish (FIN) AF: 0.0780 AC: 2497 AN: 31996

Middle Eastern (MID) AF: 0.0870 AC: 317 AN: 3642

European-Non Finnish (NFE) AF: 0.0753 AC: 25329 AN: 336376

Other (OTH) AF: 0.102 AC: 2976 AN: 29200

GnomAD4 genome AF: 0.139 AC: 21173 AN: 152040 Hom.: 1962 Cov.: 33 AF XY: 0.139 AC XY: 10305 AN XY: 74314

African (AFR) AF: 0.263 AC: 10902 AN: 41474

American (AMR) AF: 0.154 AC: 2354 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3468

East Asian (EAS) AF: 0.119 AC: 609 AN: 5132

South Asian (SAS) AF: 0.104 AC: 501 AN: 4810

European-Finnish (FIN) AF: 0.0805 AC: 853 AN: 10594

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0750 AC: 5099 AN: 67954

Other (OTH) AF: 0.121 AC: 255 AN: 2116

Alfa AF: 0.107 Hom.: 1453

Bravo AF: 0.154

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		-1.3
PromoterAI		0.010	Neutral
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: rs3734966; hg19: chr7-154862434; COSMIC: COSV55283870; COSMIC: COSV55283870;