chr21-15440893-T-C

Variant names:

• chr21-15440893-T-C
• rs1736148
• ENST00000828254.1:n.588A>G

Variant summary

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

The ENST00000828254.1(ENSG00000229425):​n.588A>G 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 0.462 in 152,012 control chromosomes in the GnomAD database, including 17,039 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 0.46 (17039 hom., cov: 32)
• Consequence: ENSG00000229425 ENST00000828254.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927745	NR_188234.1	n.341+3131A>G		intron_variant	Intron 2 of 8
LOC101927745	NR_188235.1	n.341+3131A>G		intron_variant	Intron 2 of 6
LOC101927745	NR_188236.1	n.341+3131A>G		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000229425	ENST00000828254.1	n.588A>G		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000229425	ENST00000634642.1	n.343+3131A>G		intron_variant	Intron 1 of 6	3
ENSG00000229425	ENST00000634644.1	n.952+26395A>G		intron_variant	Intron 8 of 11	5

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70165 AN: 151894 Hom.: 17002 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.462 AC: 70258 AN: 152012 Hom.: 17039 Cov.: 32 AF XY: 0.455 AC XY: 33817 AN XY: 74302

African (AFR) AF: 0.592 AC: 24527 AN: 41450

American (AMR) AF: 0.436 AC: 6654 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3468

East Asian (EAS) AF: 0.187 AC: 969 AN: 5182

South Asian (SAS) AF: 0.369 AC: 1783 AN: 4828

European-Finnish (FIN) AF: 0.394 AC: 4164 AN: 10562

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29376 AN: 67940

Other (OTH) AF: 0.462 AC: 976 AN: 2114

Alfa AF: 0.438 Hom.: 46511

Bravo AF: 0.471

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.57
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs1736148; hg19: chr21-16813212;