8-16856482-C-T

Variant names:

• chr8-16856482-C-T
• rs477516
• ENST00000521411.2:n.128-12227G>A

Variant summary

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

The ENST00000521411.2(ENSG00000253496):​n.128-12227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,018 control chromosomes in the GnomAD database, including 7,696 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 0.31 (7696 hom., cov: 32)
• Consequence: ENSG00000253496 ENST00000521411.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 6 publications found

Genes affected

ENSG00000253496 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105379297	XR_949525.1	n.157+58436G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000253496	ENST00000521411.2	n.128-12227G>A		intron_variant	Intron 1 of 3	5
ENSG00000253496	ENST00000755781.1	n.228+58436G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47299 AN: 151900 Hom.: 7696 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.311 AC: 47331 AN: 152018 Hom.: 7696 Cov.: 32 AF XY: 0.323 AC XY: 24001 AN XY: 74300

African (AFR) AF: 0.325 AC: 13464 AN: 41450

American (AMR) AF: 0.351 AC: 5365 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1987 AN: 5168

South Asian (SAS) AF: 0.532 AC: 2562 AN: 4820

European-Finnish (FIN) AF: 0.338 AC: 3569 AN: 10554

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18719 AN: 67964

Other (OTH) AF: 0.285 AC: 601 AN: 2112

Alfa AF: 0.286 Hom.: 27744

Bravo AF: 0.310

Asia WGS AF: 0.431 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.44
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs477516; hg19: chr8-16713991;