rs4535741

Variant names:

• chr8-22698911-G-T
• rs4535741
• ENST00000523627.1:n.164+8598G>T

Variant summary

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

The ENST00000523627.1(ENSG00000253125):​n.164+8598G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,294 control chromosomes in the GnomAD database, including 1,382 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 0.075 (1382 hom., cov: 31)
• Consequence: ENSG00000253125 ENST00000523627.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 2 publications found

Genes affected

ENSG00000253125 (HGNC:58186):

ENSG00000287812 (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 = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107986926	XR_001745831.3	n.424-78C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000253125	ENST00000523627.1	n.164+8598G>T		intron_variant	Intron 1 of 4	4
ENSG00000287812	ENST00000665743.1	n.2560-78C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11375 AN: 152176 Hom.: 1385 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.0551

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

GnomAD4 genome AF: 0.0748 AC: 11394 AN: 152294 Hom.: 1382 Cov.: 31 AF XY: 0.0713 AC XY: 5311 AN XY: 74472

African (AFR) AF: 0.257 AC: 10676 AN: 41530

American (AMR) AF: 0.0287 AC: 440 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00132 AC: 90 AN: 68026

Other (OTH) AF: 0.0545 AC: 115 AN: 2110

Alfa AF: 0.0513 Hom.: 289

Bravo AF: 0.0856

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.45
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs4535741; hg19: chr8-22556424;