8-23676505-G-T

Variant names:

• chr8-23676505-G-T
• rs10503733
• ENST00000835200.1:n.476-3008G>T

Variant summary

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

The ENST00000835200.1(ENSG00000308589):​n.476-3008G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,098 control chromosomes in the GnomAD database, including 5,860 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 0.27 (5860 hom., cov: 32)
• Consequence: ENSG00000308589 ENST00000835200.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 28 publications found

Genes affected

ENSG00000308589 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107986930	XR_001745842.2	n.1312+7755G>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000308589	ENST00000835200.1	n.476-3008G>T		intron_variant	Intron 4 of 4
ENSG00000308589	ENST00000835201.1	n.1098-3008G>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41612 AN: 151980 Hom.: 5857 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.274 AC: 41641 AN: 152098 Hom.: 5860 Cov.: 32 AF XY: 0.282 AC XY: 20987 AN XY: 74330

African (AFR) AF: 0.276 AC: 11454 AN: 41476

American (AMR) AF: 0.303 AC: 4637 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1453 AN: 5178

South Asian (SAS) AF: 0.329 AC: 1581 AN: 4810

European-Finnish (FIN) AF: 0.379 AC: 4008 AN: 10566

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16628 AN: 67990

Other (OTH) AF: 0.275 AC: 581 AN: 2114

Alfa AF: 0.250 Hom.: 20218

Bravo AF: 0.266

Asia WGS AF: 0.322 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.46
DANN	Benign	0.67
PhyloP100		-0.61

Splicing

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

Other links and lift over

dbSNP: rs10503733; hg19: chr8-23534018;