rs6517135

Variant names:

• chr21-33025263-T-C
• rs6517135
• ENST00000454622.2:n.201+45641A>G

Variant summary

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

The ENST00000454622.2(ENSG00000227757):​n.201+45641A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,662 control chromosomes in the GnomAD database, including 11,608 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 0.32 (11608 hom., cov: 31)
• Consequence: ENSG00000227757 ENST00000454622.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 2 publications found

Genes affected

ENSG00000227757 (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 = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000227757	ENST00000454622.2	n.201+45641A>G		intron_variant	Intron 1 of 1	2
ENSG00000227757	ENST00000777421.1	n.92-43600A>G		intron_variant	Intron 1 of 1
ENSG00000227757	ENST00000777422.1	n.108-2337A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49121 AN: 151544 Hom.: 11588 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.324 AC: 49193 AN: 151662 Hom.: 11608 Cov.: 31 AF XY: 0.324 AC XY: 23986 AN XY: 74112

African (AFR) AF: 0.674 AC: 27895 AN: 41376

American (AMR) AF: 0.238 AC: 3633 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1136 AN: 5094

South Asian (SAS) AF: 0.287 AC: 1369 AN: 4778

European-Finnish (FIN) AF: 0.187 AC: 1976 AN: 10548

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11805 AN: 67836

Other (OTH) AF: 0.288 AC: 606 AN: 2102

Alfa AF: 0.207 Hom.: 5040

Bravo AF: 0.338

Asia WGS AF: 0.305 AC: 1059 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	6.4
DANN	Benign	0.69
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs6517135; hg19: chr21-34397571;