3-87982686-G-A

Variant names:

• chr3-87982686-G-A
• rs6781226
• NM_001322209.2:c.-42-8022G>A

Variant summary

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

The NM_000866.5(HTR1F):​c.-48G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,948 control chromosomes in the GnomAD database, including 27,376 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 0.60 (27376 hom., cov: 31)
• Consequence: HTR1F NM_000866.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 2 publications found

Genes affected

HTR1F (HGNC:5292): (5-hydroxytryptamine receptor 1F) Enables G protein-coupled serotonin receptor activity and serotonin binding activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000866.5. 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
	HTR1F	NM_001322209.2	MANE Select	c.-42-8022G>A		intron	N/A	NP_001309138.1	P30939
	HTR1F	NM_000866.5		c.-48G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_000857.1	P30939
	HTR1F	NM_000866.5		c.-48G>A		5_prime_UTR	Exon 1 of 2	NP_000857.1	P30939

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1F	ENST00000319595.7	TSL:6 MANE Select	c.-42-8022G>A		intron	N/A	ENSP00000322924.4	P30939
	HTR1F	ENST00000858974.1		c.-42-8022G>A		intron	N/A	ENSP00000529033.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90710 AN: 151830 Hom.: 27351 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.598 AC: 90793 AN: 151948 Hom.: 27376 Cov.: 31 AF XY: 0.598 AC XY: 44409 AN XY: 74252

African (AFR) AF: 0.533 AC: 22111 AN: 41446

American (AMR) AF: 0.647 AC: 9884 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2299 AN: 3468

East Asian (EAS) AF: 0.699 AC: 3606 AN: 5158

South Asian (SAS) AF: 0.734 AC: 3533 AN: 4814

European-Finnish (FIN) AF: 0.555 AC: 5849 AN: 10532

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41446 AN: 67946

Other (OTH) AF: 0.612 AC: 1291 AN: 2110

Alfa AF: 0.609 Hom.: 23429

Bravo AF: 0.603

Asia WGS AF: 0.740 AC: 2572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.39
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs6781226; hg19: chr3-88031836; COSMIC: COSV59179727;