chr5-63958009-C-T

Variant names:

• chr5-63958009-C-T
• rs749099
• NM_000524.4:c.*2442G>A

Variant summary

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

The NM_000524.4(HTR1A):​c.*2442G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,086 control chromosomes in the GnomAD database, including 26,297 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 (26297 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: HTR1A NM_000524.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1A	NM_000524.4	c.*2442G>A		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.*2442G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_000524.4	ENSP00000316244.4
ENSG00000248285	ENST00000502882.1	n.103G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87584 AN: 151968 Hom.: 26256 Cov.: 33

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.572

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.576 AC: 87671 AN: 152086 Hom.: 26297 Cov.: 33 AF XY: 0.574 AC XY: 42673 AN XY: 74350

African (AFR) AF: 0.731 AC: 30325 AN: 41504

American (AMR) AF: 0.521 AC: 7960 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1858 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4097 AN: 5172

South Asian (SAS) AF: 0.589 AC: 2837 AN: 4820

European-Finnish (FIN) AF: 0.427 AC: 4500 AN: 10544

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

European-Non Finnish (NFE) AF: 0.501 AC: 34053 AN: 67966

Other (OTH) AF: 0.572 AC: 1210 AN: 2114

Alfa AF: 0.545 Hom.: 3046

Bravo AF: 0.590

Asia WGS AF: 0.668 AC: 2317 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.65
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs749099; hg19: chr5-63253836;