rs13212041

Variant names:

• chr6-77461407-C-T
• rs13212041
• NM_000863.3:c.*824G>A

Variant summary

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

The NM_000863.3(HTR1B):​c.*824G>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 0.711 in 152,004 control chromosomes in the GnomAD database, including 40,319 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 0.71 (40319 hom., cov: 31)
• Consequence: HTR1B NM_000863.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 64 publications found

Genes affected

HTR1B (HGNC:5287): (5-hydroxytryptamine receptor 1B) The protein encoded by this intronless gene is a G-protein coupled receptor for serotonin (5-hydroxytryptamine). Ligand binding activates second messengers that inhibit the activity of adenylate cyclase and manage the release of serotonin, dopamine, and acetylcholine in the brain. The encoded protein may be involved in several neuropsychiatric disorders and therefore is often a target of antidepressant and other psychotherapeutic drugs. [provided by RefSeq, Nov 2015]

ENSG00000296734 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1B	NM_000863.3	c.*824G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000369947.5	NP_000854.1
LOC105377864	XM_047419660.1	c.-3742-13119C>T		intron_variant	Intron 5 of 8		XP_047275616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1B	ENST00000369947.5	c.*824G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_000863.3	ENSP00000358963.3
ENSG00000296734	ENST00000741460.1	n.48+5493G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108058 AN: 151886 Hom.: 40316 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.711 AC: 108084 AN: 152004 Hom.: 40319 Cov.: 31 AF XY: 0.716 AC XY: 53210 AN XY: 74306

African (AFR) AF: 0.465 AC: 19250 AN: 41388

American (AMR) AF: 0.819 AC: 12514 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 3006 AN: 3470

East Asian (EAS) AF: 0.757 AC: 3911 AN: 5166

South Asian (SAS) AF: 0.865 AC: 4168 AN: 4820

European-Finnish (FIN) AF: 0.800 AC: 8457 AN: 10572

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54149 AN: 67992

Other (OTH) AF: 0.753 AC: 1587 AN: 2108

Alfa AF: 0.749 Hom.: 85714

Bravo AF: 0.701

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		2.2

Splicing

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

Other links and lift over

dbSNP: rs13212041; hg19: chr6-78171124;