6-77462224-C-T

Position:

• chr6-77462224-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000863.3(HTR1B):​c.*7G>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 0.867 in 1,598,622 control chromosomes in the GnomAD database, including 602,363 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 0.90 (61975 hom., cov: 33)
  • Exomes 𝑓: 0.86 (540388 hom.)
• Consequence: HTR1B NM_000863.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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]

LOC105377864 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR1B	NM_000863.3	c.*7G>A		3_prime_UTR_variant	1/1	ENST00000369947.5	NP_000854.1
LOC105377864	XM_047419659.1	c.-12000C>T		5_prime_UTR_premature_start_codon_gain_variant	1/6		XP_047275615.1
LOC105377864	XM_047419659.1	c.-12000C>T		5_prime_UTR_variant	1/6		XP_047275615.1
LOC105377864	XM_047419660.1	c.-3742-12302C>T		intron_variant			XP_047275616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR1B	ENST00000369947	c.*7G>A		3_prime_UTR_variant	1/1		NM_000863.3	ENSP00000358963.3

Frequencies

GnomAD3 genomes AF: 0.900 AC: 137011 AN: 152152 Hom.: 61923 Cov.: 33

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.918

GnomAD3 exomes AF: 0.891 AC: 220330 AN: 247382 Hom.: 98414 AF XY: 0.891 AC XY: 118958 AN XY: 133568

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.935

Gnomad ASJ exome AF: 0.968

Gnomad EAS exome AF: 0.886

Gnomad SAS exome AF: 0.927

Gnomad FIN exome AF: 0.859

Gnomad NFE exome AF: 0.855

Gnomad OTH exome AF: 0.900

GnomAD4 exome AF: 0.863 AC: 1248875 AN: 1446352 Hom.: 540388 Cov.: 30 AF XY: 0.865 AC XY: 621280 AN XY: 718132

Gnomad4 AFR exome AF: 0.979

Gnomad4 AMR exome AF: 0.934

Gnomad4 ASJ exome AF: 0.964

Gnomad4 EAS exome AF: 0.856

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.862

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.887

GnomAD4 genome AF: 0.901 AC: 137121 AN: 152270 Hom.: 61975 Cov.: 33 AF XY: 0.903 AC XY: 67246 AN XY: 74444

Gnomad4 AFR AF: 0.973

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.916

Alfa AF: 0.885 Hom.: 27550

Bravo AF: 0.909

Asia WGS AF: 0.905 AC: 3150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs6297; hg19: chr6-78171941;