6-31730575-T-C

Position:

• chr6-31730575-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375792.7(DDAH2):​c.-589A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 484,664 control chromosomes in the GnomAD database, including 180,895 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 (59013 hom., cov: 32)
  • Exomes 𝑓: 0.85 (121882 hom.)
• Consequence: DDAH2 ENST00000375792.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62

Genes affected

DDAH2 (HGNC:2716): (DDAH family member 2, ADMA-independent) This gene encodes a dimethylarginine dimethylaminohydrolase. The encoded enzyme functions in nitric oxide generation by regulating the cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. The protein may be localized to the mitochondria. Alternative splicing resulting in multiple transcript variants. [provided by RefSeq, Dec 2014]

(HGNC:):

CLIC1 (HGNC:2062): (chloride intracellular channel 1) Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.31730575T>C		intergenic_region
CLIC1	NM_001288.6	c.*267A>G		downstream_gene_variant		ENST00000375784.8	NP_001279.2
CLIC1	NM_001287593.1	c.*267A>G		downstream_gene_variant			NP_001274522.1
CLIC1	NM_001287594.3	c.*267A>G		downstream_gene_variant			NP_001274523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIC1	ENST00000375784.8	c.*267A>G		downstream_gene_variant		1	NM_001288.6	ENSP00000364940.3

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133535 AN: 152092 Hom.: 58952 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.904

GnomAD4 exome AF: 0.854 AC: 283862 AN: 332454 Hom.: 121882 Cov.: 3 AF XY: 0.857 AC XY: 148428 AN XY: 173158

Gnomad4 AFR exome AF: 0.967

Gnomad4 AMR exome AF: 0.922

Gnomad4 ASJ exome AF: 0.933

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.904

Gnomad4 FIN exome AF: 0.838

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.859

GnomAD4 genome AF: 0.878 AC: 133656 AN: 152210 Hom.: 59013 Cov.: 32 AF XY: 0.879 AC XY: 65390 AN XY: 74424

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.903

Alfa AF: 0.832 Hom.: 57152

Bravo AF: 0.887

Asia WGS AF: 0.897 AC: 3121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.12
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272592; hg19: chr6-31698352;