10-8591898-C-T

Variant names:

• chr10-8591898-C-T
• rs4749791
• ENST00000750865.1:n.303-18498G>A

Variant summary

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

The ENST00000750865.1(ENSG00000297769):​n.303-18498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,866 control chromosomes in the GnomAD database, including 8,937 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 0.33 (8937 hom., cov: 32)
• Consequence: ENSG00000297769 ENST00000750865.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 6 publications found

Genes affected

ENSG00000297769 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376398	NR_134492.1	n.44+2450G>A		intron_variant	Intron 1 of 1
LOC105376399	XR_001747362.2	n.162+26C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000297769	ENST00000750865.1	n.303-18498G>A		intron_variant	Intron 3 of 3
ENSG00000297769	ENST00000750866.1	n.155-18498G>A		intron_variant	Intron 2 of 2
ENSG00000297769	ENST00000750867.1	n.87+2450G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49674 AN: 151748 Hom.: 8907 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.328 AC: 49760 AN: 151866 Hom.: 8937 Cov.: 32 AF XY: 0.329 AC XY: 24401 AN XY: 74210

African (AFR) AF: 0.449 AC: 18598 AN: 41428

American (AMR) AF: 0.376 AC: 5725 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3472

East Asian (EAS) AF: 0.395 AC: 2029 AN: 5140

South Asian (SAS) AF: 0.488 AC: 2343 AN: 4800

European-Finnish (FIN) AF: 0.217 AC: 2287 AN: 10536

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16686 AN: 67932

Other (OTH) AF: 0.312 AC: 660 AN: 2116

Alfa AF: 0.290 Hom.: 13732

Bravo AF: 0.342

Asia WGS AF: 0.484 AC: 1680 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.057
DANN	Benign	0.50
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs4749791; hg19: chr10-8633861;