8-88535703-C-T

Variant names:

• chr8-88535703-C-T
• rs10504861
• ENST00000521433.1:n.180-6977C>T

Variant summary

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

The ENST00000521433.1(ENSG00000253553):​n.180-6977C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,016 control chromosomes in the GnomAD database, including 4,278 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 0.22 (4278 hom., cov: 32)
• Consequence: ENSG00000253553 ENST00000521433.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 24 publications found

Genes affected

ENSG00000253553 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375629	XR_001745651.3	n.676+10814G>A		intron_variant	Intron 6 of 6
LOC105375630	XR_001745653.3	n.225-6977C>T		intron_variant	Intron 2 of 7
LOC105375630	XR_007060996.1	n.180-6977C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000253553	ENST00000521433.1	n.180-6977C>T		intron_variant	Intron 2 of 4	4
ENSG00000253553	ENST00000658256.1	n.285-164589C>T		intron_variant	Intron 2 of 3
ENSG00000253553	ENST00000658283.1	n.426-6977C>T		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33826 AN: 151898 Hom.: 4273 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.223 AC: 33850 AN: 152016 Hom.: 4278 Cov.: 32 AF XY: 0.221 AC XY: 16398 AN XY: 74284

African (AFR) AF: 0.344 AC: 14259 AN: 41480

American (AMR) AF: 0.171 AC: 2610 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3466

East Asian (EAS) AF: 0.107 AC: 554 AN: 5162

South Asian (SAS) AF: 0.199 AC: 954 AN: 4806

European-Finnish (FIN) AF: 0.162 AC: 1711 AN: 10562

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12354 AN: 67960

Other (OTH) AF: 0.226 AC: 477 AN: 2112

Alfa AF: 0.198 Hom.: 4739

Bravo AF: 0.226

Asia WGS AF: 0.182 AC: 629 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.55
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs10504861; hg19: chr8-89547932;