8-92470335-T-G

Variant names:

• chr8-92470335-T-G
• rs2046129
• ENST00000648652.1:n.1195+1388A>C

Variant summary

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

The ENST00000648652.1(ENSG00000253634):​n.1195+1388A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,160 control chromosomes in the GnomAD database, including 9,719 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 0.35 (9719 hom., cov: 33)
• Consequence: ENSG00000253634 ENST00000648652.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 1 publications found

Genes affected

ENSG00000253634 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375639	XR_007061005.1	n.568+1388A>C		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000253634	ENST00000648652.1	n.1195+1388A>C		intron_variant	Intron 9 of 13
ENSG00000253634	ENST00000744168.1	n.540+1388A>C		intron_variant	Intron 5 of 6
ENSG00000253634	ENST00000744176.1	n.100-4684A>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53834 AN: 152042 Hom.: 9715 Cov.: 33

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.354 AC: 53876 AN: 152160 Hom.: 9719 Cov.: 33 AF XY: 0.350 AC XY: 26062 AN XY: 74396

African (AFR) AF: 0.441 AC: 18302 AN: 41498

American (AMR) AF: 0.311 AC: 4758 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1142 AN: 5176

South Asian (SAS) AF: 0.241 AC: 1165 AN: 4826

European-Finnish (FIN) AF: 0.328 AC: 3471 AN: 10576

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22420 AN: 68010

Other (OTH) AF: 0.323 AC: 682 AN: 2112

Alfa AF: 0.244 Hom.: 813

Bravo AF: 0.359

Asia WGS AF: 0.225 AC: 783 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.57
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs2046129; hg19: chr8-93482563;