chr6-77463665-A-C

Variant names:

• chr6-77463665-A-C
• rs11568817
• XM_047419659.1:c.-10794A>C

Variant summary

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

The XM_047419659.1(LOC105377864):​c.-10794A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 565,208 control chromosomes in the GnomAD database, including 50,950 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 0.37 (11621 hom., cov: 32)
  • Exomes 𝑓: 0.42 (39329 hom.)
• Consequence: LOC105377864 XM_047419659.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

LOC105377864 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1B	NM_000863.3	c.-262T>G		upstream_gene_variant		ENST00000369947.5	NP_000854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1B	ENST00000369947.5	c.-262T>G		upstream_gene_variant		6	NM_000863.3	ENSP00000358963.3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55967 AN: 151784 Hom.: 11621 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.423 AC: 174763 AN: 413304 Hom.: 39329 Cov.: 2 AF XY: 0.427 AC XY: 92270 AN XY: 216340

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.541

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.369 AC: 56005 AN: 151904 Hom.: 11621 Cov.: 32 AF XY: 0.371 AC XY: 27544 AN XY: 74224

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.414

Alfa AF: 0.397 Hom.: 1661

Bravo AF: 0.354

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.7
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11568817; hg19: chr6-78173382;