chr1-19666992-A-G

Variant names:

• chr1-19666992-A-G
• rs4912138
• NM_000871.3:c.714+525A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000871.3(HTR6):​c.714+525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 151,764 control chromosomes in the GnomAD database, including 46,288 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 0.78 (46288 hom., cov: 29)
• Consequence: HTR6 NM_000871.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 11 publications found

Genes affected

HTR6 (HGNC:5301): (5-hydroxytryptamine receptor 6) This gene encodes a protein that belongs to the seven-transmembrane G protein-coupled receptor family of proteins. The encoded protein couples with the Gs alpha subunit and stimulates adenylate cyclase to activate the cyclic AMP-dependent signaling pathway. This receptor is thought to regulate cholinergic neuronal transmission in the brain. Several antidepressants and antipsychotic drugs have a high affinity for this receptor. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000871.3. 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
	HTR6	NM_000871.3	MANE Select	c.714+525A>G		intron	N/A	NP_000862.1	P50406

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR6	ENST00000289753.2	TSL:1 MANE Select	c.714+525A>G		intron	N/A	ENSP00000289753.1	P50406

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118041 AN: 151646 Hom.: 46240 Cov.: 29

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.756

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.779 AC: 118149 AN: 151764 Hom.: 46288 Cov.: 29 AF XY: 0.774 AC XY: 57435 AN XY: 74182

African (AFR) AF: 0.795 AC: 32914 AN: 41384

American (AMR) AF: 0.706 AC: 10762 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2656 AN: 3466

East Asian (EAS) AF: 0.478 AC: 2446 AN: 5112

South Asian (SAS) AF: 0.740 AC: 3534 AN: 4776

European-Finnish (FIN) AF: 0.822 AC: 8694 AN: 10574

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54657 AN: 67904

Other (OTH) AF: 0.758 AC: 1594 AN: 2104

Alfa AF: 0.778 Hom.: 26330

Bravo AF: 0.772

Asia WGS AF: 0.641 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.19
DANN	Benign	0.57
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4912138; hg19: chr1-19993485;