12-9311210-T-C

Variant names:

• chr12-9311210-T-C
• rs10771515
• ENST00000539757.1:n.2325T>C

Variant summary

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

The ENST00000539757.1(DDX12B):​n.2325T>C 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 0.94 in 1,389,540 control chromosomes in the GnomAD database, including 617,689 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 0.91 (62918 hom., cov: 26)
  • Exomes 𝑓: 0.94 (554771 hom.)
• Consequence: DDX12B ENST00000539757.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58
• Publications: 8 publications found

Genes affected

DDX12B (HGNC:38668): (DEAD/H-box helicase 12B%2C pseudogene [Source:HGNC Symbol%3BAcc:HGNC:38668])

LOC642846 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC642846	NR_024374.1	n.2435T>C		non_coding_transcript_exon_variant	Exon 21 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX12B	ENST00000539757.1	n.2325T>C		non_coding_transcript_exon_variant	Exon 22 of 29	6
ENSG00000299001	ENST00000759736.1	n.139+1831A>G		intron_variant	Intron 1 of 1
ENSG00000299001	ENST00000759737.1	n.108+1831A>G		intron_variant	Intron 1 of 2
ENSG00000299001	ENST00000759738.1	n.165-1747A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.911 AC: 137337 AN: 150750 Hom.: 62874 Cov.: 26

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.896

GnomAD4 exome AF: 0.944 AC: 1169282 AN: 1238674 Hom.: 554771 Cov.: 20 AF XY: 0.946 AC XY: 592119 AN XY: 626238

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

African (AFR) AF: 0.829 AC: 24072 AN: 29028

American (AMR) AF: 0.953 AC: 41791 AN: 43846

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 23613 AN: 24506

East Asian (EAS) AF: 0.744 AC: 28353 AN: 38094

South Asian (SAS) AF: 0.962 AC: 78648 AN: 81784

European-Finnish (FIN) AF: 0.950 AC: 50212 AN: 52834

Middle Eastern (MID) AF: 0.944 AC: 4938 AN: 5232

European-Non Finnish (NFE) AF: 0.954 AC: 868436 AN: 910644

Other (OTH) AF: 0.934 AC: 49219 AN: 52706

⚠️ 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: 0.911 AC: 137432 AN: 150866 Hom.: 62918 Cov.: 26 AF XY: 0.910 AC XY: 67067 AN XY: 73666

African (AFR) AF: 0.835 AC: 34171 AN: 40946

American (AMR) AF: 0.937 AC: 14261 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3365 AN: 3464

East Asian (EAS) AF: 0.712 AC: 3583 AN: 5030

South Asian (SAS) AF: 0.957 AC: 4534 AN: 4738

European-Finnish (FIN) AF: 0.950 AC: 9997 AN: 10522

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64473 AN: 67658

Other (OTH) AF: 0.895 AC: 1870 AN: 2090

Alfa AF: 0.926 Hom.: 16624

Bravo AF: 0.903

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.55
PhyloP100		3.6

Splicing

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

Other links and lift over

dbSNP: rs10771515; hg19: chr12-9463806; COSMIC: COSV62037025;