2-240582850-A-T

Variant names:

• chr2-240582850-A-T
• rs1133353
• ENST00000567819.1:n.3850T>A

Variant summary

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

The ENST00000567819.1(CAPN10-DT):​n.3850T>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 0.859 in 152,004 control chromosomes in the GnomAD database, including 56,201 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 0.86 (56199 hom., cov: 34)
  • Exomes 𝑓: 0.83 (2 hom.)
• Consequence: CAPN10-DT ENST00000567819.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33
• Publications: 10 publications found

Genes affected

CAPN10-DT (HGNC:48839): (CAPN10 divergent transcript)

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 (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN10-DT	NR_103792.1	n.3467T>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN10-DT	ENST00000567819.1	n.3850T>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
CAPN10-DT	ENST00000791520.1	n.709T>A		non_coding_transcript_exon_variant	Exon 3 of 3
CAPN10-DT	ENST00000791521.1	n.242T>A		non_coding_transcript_exon_variant	Exon 2 of 2
CAPN10-DT	ENST00000791519.1	n.376-1175T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130486 AN: 151880 Hom.: 56146 Cov.: 34

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.845

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 2 Cov.: 0 AF XY: 0.750 AC XY: 3 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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.859 AC: 130598 AN: 151998 Hom.: 56199 Cov.: 34 AF XY: 0.861 AC XY: 63936 AN XY: 74294

African (AFR) AF: 0.841 AC: 34827 AN: 41408

American (AMR) AF: 0.881 AC: 13481 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2771 AN: 3468

East Asian (EAS) AF: 0.987 AC: 5114 AN: 5180

South Asian (SAS) AF: 0.829 AC: 4003 AN: 4830

European-Finnish (FIN) AF: 0.881 AC: 9295 AN: 10554

Middle Eastern (MID) AF: 0.747 AC: 215 AN: 288

European-Non Finnish (NFE) AF: 0.858 AC: 58277 AN: 67950

Other (OTH) AF: 0.847 AC: 1790 AN: 2114

Alfa AF: 0.861 Hom.: 7032

Bravo AF: 0.860

Asia WGS AF: 0.905 AC: 3150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.53
DANN	Benign	0.22
PhyloP100		-3.3

Splicing

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

Other links and lift over

dbSNP: rs1133353; hg19: chr2-241522267;