XM_047419659.1:c.-10895T>G

Variant names:

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

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>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000608 in 673,808 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: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000065 (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=-0.57).

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

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151908 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000651 AC: 34 AN: 521900 Hom.: 0 Cov.: 6 AF XY: 0.0000553 AC XY: 15 AN XY: 271468

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

American (AMR) AF: 0.0000535 AC: 1 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: 0.0000949 AC: 32 AN: 337122

Other (OTH) AF: 0.0000351 AC: 1 AN: 28498

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151908 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74182

African (AFR) AF: 0.00 AC: 0 AN: 41308

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2094

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	-0.57
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		-0.68
PromoterAI		-0.12	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;