9-35815616-G-T

Variant names:

• chr9-35815616-G-T
• rs3808864
• ENST00000650284.1:n.*556-1832C>A

Variant summary

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

The ENST00000650284.1(ENSG00000285645):​n.*556-1832C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,990 control chromosomes in the GnomAD database, including 45,130 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 0.74 (45130 hom., cov: 31)
• Consequence: ENSG00000285645 ENST00000650284.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 5 publications found

Genes affected

ENSG00000285645 (HGNC:):

TMEM8B (HGNC:21427): (transmembrane protein 8B) Involved in cell-matrix adhesion. Located in cell surface and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

HINT2 (HGNC:18344): (histidine triad nucleotide binding protein 2) Histidine triad proteins, such as HINT2, are nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides (Brenner, 2002 [PubMed 12119013]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HINT2	XM_024447702.2	c.-401C>A		upstream_gene_variant			XP_024303470.1
HINT2	XM_024447703.1	c.-401C>A		upstream_gene_variant			XP_024303471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285645	ENST00000650284.1	n.*556-1832C>A		intron_variant	Intron 6 of 9			ENSP00000498023.1
TMEM8B	ENST00000377996.5	c.-542+292G>T		intron_variant	Intron 1 of 8	2		ENSP00000367235.1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112018 AN: 151872 Hom.: 45123 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.737 AC: 112063 AN: 151990 Hom.: 45130 Cov.: 31 AF XY: 0.737 AC XY: 54747 AN XY: 74314

African (AFR) AF: 0.377 AC: 15611 AN: 41388

American (AMR) AF: 0.824 AC: 12597 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2952 AN: 3472

East Asian (EAS) AF: 0.754 AC: 3890 AN: 5156

South Asian (SAS) AF: 0.856 AC: 4127 AN: 4822

European-Finnish (FIN) AF: 0.823 AC: 8701 AN: 10576

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61382 AN: 67986

Other (OTH) AF: 0.799 AC: 1679 AN: 2102

Alfa AF: 0.859 Hom.: 29072

Bravo AF: 0.722

Asia WGS AF: 0.767 AC: 2669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.40
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3808864; hg19: chr9-35815613;