rs6449693

Variant names:

• chr5-63960191-G-A
• rs6449693
• NM_000524.4:c.*260C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-63960191-G-A
• chr5-63960191-G-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.*260C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,100 control chromosomes in the GnomAD database, including 26,419 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 0.58 (26419 hom., cov: 33)
• Consequence: HTR1A NM_000524.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• Publications: 18 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1A	NM_000524.4	c.*260C>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000323865.5	NP_000515.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1A	ENST00000323865.5	c.*260C>T		3_prime_UTR_variant	Exon 1 of 1	6	NM_000524.4	ENSP00000316244.4
ENSG00000248285	ENST00000502882.1	n.97-2176C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87733 AN: 151982 Hom.: 26373 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.577 AC: 87827 AN: 152100 Hom.: 26419 Cov.: 33 AF XY: 0.575 AC XY: 42745 AN XY: 74354

African (AFR) AF: 0.735 AC: 30491 AN: 41510

American (AMR) AF: 0.521 AC: 7966 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1858 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4086 AN: 5162

South Asian (SAS) AF: 0.589 AC: 2842 AN: 4822

European-Finnish (FIN) AF: 0.426 AC: 4496 AN: 10556

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34046 AN: 67964

Other (OTH) AF: 0.573 AC: 1212 AN: 2114

Alfa AF: 0.519 Hom.: 53354

Bravo AF: 0.591

Asia WGS AF: 0.669 AC: 2325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.27
DANN	Benign	0.74
PhyloP100		-0.95

Splicing

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

Other links and lift over

dbSNP: rs6449693; hg19: chr5-63256018;