6-77462224-C-T

Variant names:

• chr6-77462224-C-T
• rs6297
• NM_000863.3:c.*7G>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.*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
• Publications: 34 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]

LOC105377864 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HTR1B	NM_000863.3	c.*7G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000369947.5	NP_000854.1
LOC105377864	XM_047419659.1	c.-12000C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6		XP_047275615.1
LOC105377864	XM_047419659.1	c.-12000C>T		5_prime_UTR_variant	Exon 1 of 6		XP_047275615.1
LOC105377864	XM_047419660.1	c.-3742-12302C>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.*7G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_000863.3	ENSP00000358963.3
ENSG00000296734	ENST00000741460.1	n.48+4676G>A		intron_variant	Intron 1 of 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

GnomAD2 exomes AF: 0.891 AC: 220330 AN: 247382 AF XY: 0.891

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 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

African (AFR) AF: 0.979 AC: 32422 AN: 33106

American (AMR) AF: 0.934 AC: 41308 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 24747 AN: 25658

East Asian (EAS) AF: 0.856 AC: 33793 AN: 39496

South Asian (SAS) AF: 0.928 AC: 79089 AN: 85182

European-Finnish (FIN) AF: 0.862 AC: 45816 AN: 53122

Middle Eastern (MID) AF: 0.979 AC: 5566 AN: 5684

European-Non Finnish (NFE) AF: 0.848 AC: 933204 AN: 1100206

Other (OTH) AF: 0.887 AC: 52930 AN: 59688

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

African (AFR) AF: 0.973 AC: 40435 AN: 41568

American (AMR) AF: 0.934 AC: 14298 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3333 AN: 3472

East Asian (EAS) AF: 0.884 AC: 4553 AN: 5150

South Asian (SAS) AF: 0.926 AC: 4469 AN: 4828

European-Finnish (FIN) AF: 0.869 AC: 9215 AN: 10610

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57760 AN: 68016

Other (OTH) AF: 0.916 AC: 1934 AN: 2112

Alfa AF: 0.882 Hom.: 35550

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
PhyloP100		-0.31
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs6297; hg19: chr6-78171941;