21-15523514-G-T

Variant names:

• chr21-15523514-G-T
• rs2823324
• ENST00000635525.2:n.3612C>A

Variant summary

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

The ENST00000635525.2(ENSG00000229425):​n.3612C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,160 control chromosomes in the GnomAD database, including 3,218 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 0.13 (3217 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1 hom.)
• Consequence: ENSG00000229425 ENST00000635525.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 0 publications found

Genes affected

ENSG00000229425 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369302	XR_001754972.2	n.3566C>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000229425	ENST00000635525.2	n.3612C>A		non_coding_transcript_exon_variant	Exon 3 of 3	5
ENSG00000229425	ENST00000657904.1	n.1650C>A		non_coding_transcript_exon_variant	Exon 3 of 3
ENSG00000229425	ENST00000669763.2	n.3731C>A		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19703 AN: 151944 Hom.: 3197 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0680

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0306 AC: 3 AN: 98 Hom.: 1 Cov.: 0 AF XY: 0.0256 AC XY: 2 AN XY: 78

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0233 AC: 2 AN: 86

Other (OTH) AF: 0.125 AC: 1 AN: 8

GnomAD4 genome AF: 0.130 AC: 19780 AN: 152062 Hom.: 3217 Cov.: 32 AF XY: 0.127 AC XY: 9443 AN XY: 74362

African (AFR) AF: 0.383 AC: 15843 AN: 41388

American (AMR) AF: 0.0761 AC: 1164 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3468

East Asian (EAS) AF: 0.140 AC: 726 AN: 5170

South Asian (SAS) AF: 0.0681 AC: 328 AN: 4818

European-Finnish (FIN) AF: 0.00650 AC: 69 AN: 10612

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0189 AC: 1285 AN: 67998

Other (OTH) AF: 0.100 AC: 211 AN: 2106

Alfa AF: 0.0479 Hom.: 1382

Bravo AF: 0.147

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.28
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs2823324; hg19: chr21-16895833;