21-27372037-A-G

Variant names:

• chr21-27372037-A-G
• rs1452093
• ENST00000420186.2:n.332-10881T>C

Variant summary

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

The ENST00000420186.2(ENSG00000231236):​n.332-10881T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,940 control chromosomes in the GnomAD database, including 18,368 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 (18368 hom., cov: 32)
• Consequence: ENSG00000231236 ENST00000420186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 15 publications found

Genes affected

ENSG00000231236 (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 (NFE) allele frequency at 95% confidence interval = 0.603 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
ENSG00000231236	ENST00000420186.2	n.332-10881T>C		intron_variant	Intron 3 of 3	1
ENSG00000236332	ENST00000447384.1	n.391+9224A>G		intron_variant	Intron 2 of 4	1
ENSG00000236332	ENST00000656258.2	n.434+9224A>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70504 AN: 151822 Hom.: 18350 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.464 AC: 70538 AN: 151940 Hom.: 18368 Cov.: 32 AF XY: 0.458 AC XY: 34040 AN XY: 74248

African (AFR) AF: 0.248 AC: 10279 AN: 41472

American (AMR) AF: 0.445 AC: 6776 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1743 AN: 3470

East Asian (EAS) AF: 0.174 AC: 901 AN: 5172

South Asian (SAS) AF: 0.572 AC: 2757 AN: 4820

European-Finnish (FIN) AF: 0.494 AC: 5210 AN: 10540

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41277 AN: 67922

Other (OTH) AF: 0.469 AC: 990 AN: 2110

Alfa AF: 0.541 Hom.: 46967

Bravo AF: 0.443

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.62
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs1452093; hg19: chr21-28744356;