chr1-85442168-A-T

Position:

• chr1-85442168-A-T

Variant summary

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

The NM_012137.4(DDAH1):​c.303+22575T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,042 control chromosomes in the GnomAD database, including 56,477 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 (56477 hom., cov: 30)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

Genes affected

DDAH1 (HGNC:2715): (dimethylarginine dimethylaminohydrolase 1) This gene belongs to the dimethylarginine dimethylaminohydrolase (DDAH) gene family. The encoded enzyme plays a role in nitric oxide generation by regulating cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. [provided by RefSeq, Jul 2008]

BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+22575T>A		intron_variant		ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.303+22575T>A		intron_variant		1	NM_012137.4	ENSP00000284031	P1
DDAH1	ENST00000426972.8	c.-7+53998T>A		intron_variant		1		ENSP00000411189
BCL10-AS1	ENST00000426125.1	n.138-5630A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130734 AN: 151924 Hom.: 56420 Cov.: 30

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.861 AC: 130850 AN: 152042 Hom.: 56477 Cov.: 30 AF XY: 0.858 AC XY: 63751 AN XY: 74302

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.890

Alfa AF: 0.846 Hom.: 6766

Bravo AF: 0.872

Asia WGS AF: 0.813 AC: 2830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.90
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs499869; hg19: chr1-85907851;