chr6-77463665-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 51 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369947.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1B	NM_000863.3	MANE Select	c.-262T>G		upstream_gene	N/A	NP_000854.1	P28222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000296734	ENST00000741460.1		n.48+3235T>G		intron	N/A
	HTR1B	ENST00000369947.5	TSL:6 MANE Select	c.-262T>G		upstream_gene	N/A	ENSP00000358963.3	P28222

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

African (AFR) AF: 0.193 AC: 2278 AN: 11832

American (AMR) AF: 0.394 AC: 6508 AN: 16516

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 7013 AN: 12956

East Asian (EAS) AF: 0.104 AC: 3007 AN: 29030

South Asian (SAS) AF: 0.464 AC: 18237 AN: 39308

European-Finnish (FIN) AF: 0.463 AC: 12685 AN: 27390

Middle Eastern (MID) AF: 0.562 AC: 1038 AN: 1846

European-Non Finnish (NFE) AF: 0.454 AC: 113573 AN: 250148

Other (OTH) AF: 0.429 AC: 10424 AN: 24278

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

African (AFR) AF: 0.200 AC: 8287 AN: 41418

American (AMR) AF: 0.389 AC: 5943 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1855 AN: 3472

East Asian (EAS) AF: 0.125 AC: 642 AN: 5116

South Asian (SAS) AF: 0.456 AC: 2191 AN: 4806

European-Finnish (FIN) AF: 0.482 AC: 5097 AN: 10568

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30546 AN: 67926

Other (OTH) AF: 0.414 AC: 874 AN: 2110

Alfa AF: 0.403 Hom.: 19069

Bravo AF: 0.354

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.7
DANN	Benign	0.64
PhyloP100		-0.17
PromoterAI		0.040	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11568817; hg19: chr6-78173382;