rs749098

Variant names:

• chr5-63958465-C-G
• rs749098
• NM_000524.4:c.*1986G>C

Variant summary

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

The NM_000524.4(HTR1A):​c.*1986G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,094 control chromosomes in the GnomAD database, including 5,150 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 0.25 (5150 hom., cov: 33)
• Consequence: HTR1A NM_000524.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496
• Publications: 3 publications found

Genes affected

HTR1A (HGNC:5286): (5-hydroxytryptamine receptor 1A) This gene encodes a G protein-coupled receptor for 5-hydroxytryptamine (serotonin), and belongs to the 5-hydroxytryptamine receptor subfamily. Serotonin has been implicated in a number of physiologic processes and pathologic conditions. Inactivation of this gene in mice results in behavior consistent with an increased anxiety and stress response. Mutation in the promoter of this gene has been associated with menstrual cycle-dependent periodic fevers. [provided by RefSeq, Jun 2012]

HTR1A Gene-Disease associations (from GenCC):

• menstrual cycle-dependent periodic fever

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000248285 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000524.4. 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
	HTR1A	NM_000524.4	MANE Select	c.*1986G>C		3_prime_UTR	Exon 1 of 1	NP_000515.2	P08908

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1A	ENST00000323865.5	TSL:6 MANE Select	c.*1986G>C		3_prime_UTR	Exon 1 of 1	ENSP00000316244.4	P08908
	ENSG00000248285	ENST00000502882.1	TSL:2	n.97-450G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37709 AN: 151976 Hom.: 5140 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.248 AC: 37719 AN: 152094 Hom.: 5150 Cov.: 33 AF XY: 0.252 AC XY: 18752 AN XY: 74342

African (AFR) AF: 0.211 AC: 8745 AN: 41502

American (AMR) AF: 0.252 AC: 3853 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 990 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3244 AN: 5166

South Asian (SAS) AF: 0.370 AC: 1783 AN: 4818

European-Finnish (FIN) AF: 0.225 AC: 2375 AN: 10578

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15751 AN: 67956

Other (OTH) AF: 0.249 AC: 527 AN: 2116

Alfa AF: 0.238 Hom.: 576

Bravo AF: 0.245

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.49
PhyloP100		0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs749098; hg19: chr5-63254292;