chr6-77463564-T-C

Variant names:

• chr6-77463564-T-C
• rs130058
• XM_047419659.1:c.-10895T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XM_047419659.1(LOC105377864):​c.-10895T>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 0.00000192 in 521,900 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: LOC105377864 XM_047419659.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 79 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

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.-161A>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+3336A>G		intron	N/A
	HTR1B	ENST00000369947.5	TSL:6 MANE Select	c.-161A>G		upstream_gene	N/A	ENSP00000358963.3	P28222

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000192 AC: 1 AN: 521900 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 271468

African (AFR) AF: 0.00 AC: 0 AN: 13756

American (AMR) AF: 0.00 AC: 0 AN: 18680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14160

East Asian (EAS) AF: 0.00 AC: 0 AN: 31424

South Asian (SAS) AF: 0.00 AC: 0 AN: 46484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2154

European-Non Finnish (NFE) AF: 0.00000297 AC: 1 AN: 337122

Other (OTH) AF: 0.00 AC: 0 AN: 28498

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		-0.68
PromoterAI		0.0064	Neutral

Splicing

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

Other links and lift over

dbSNP: rs130058; hg19: chr6-78173281;