21-42831113-T-C

Variant names:

• chr21-42831113-T-C
• rs2839586
• ENST00000431150.1:n.212A>G

Variant summary

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

The ENST00000431150.1(ENSG00000225218):​n.212A>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 0.881 in 152,282 control chromosomes in the GnomAD database, including 59,190 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 0.88 (59190 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENSG00000225218 ENST00000431150.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 7 publications found

Genes affected

ENSG00000225218 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 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
ENSG00000225218	ENST00000431150.1	n.212A>G		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.881 AC: 134058 AN: 152160 Hom.: 59146 Cov.: 33

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.885

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.002339), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.881 AC: 134159 AN: 152278 Hom.: 59190 Cov.: 33 AF XY: 0.874 AC XY: 65108 AN XY: 74458

African (AFR) AF: 0.929 AC: 38601 AN: 41566

American (AMR) AF: 0.886 AC: 13553 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3079 AN: 3470

East Asian (EAS) AF: 0.762 AC: 3949 AN: 5182

South Asian (SAS) AF: 0.795 AC: 3827 AN: 4816

European-Finnish (FIN) AF: 0.811 AC: 8608 AN: 10608

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59614 AN: 68016

Other (OTH) AF: 0.880 AC: 1861 AN: 2114

Alfa AF: 0.873 Hom.: 29259

Bravo AF: 0.888

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		0.013

Splicing

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

Other links and lift over

dbSNP: rs2839586; hg19: chr21-44251223;