7-107895853-A-G

Position:

• chr7-107895853-A-G

Variant summary

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

The NM_000108.5(DLD):​c.118+2575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,142 control chromosomes in the GnomAD database, including 34,002 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 0.66 (34002 hom., cov: 32)
• Consequence: DLD NM_000108.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582

Genes affected

DLD (HGNC:2898): (dihydrolipoamide dehydrogenase) This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DLD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLD	NM_000108.5	c.118+2575A>G		intron_variant		ENST00000205402.10	NP_000099.2
DLD	NM_001289751.1	c.118+2575A>G		intron_variant			NP_001276680.1
DLD	NM_001289752.1	c.118+2575A>G		intron_variant			NP_001276681.1
DLD	NM_001289750.1	c.-31+2575A>G		intron_variant			NP_001276679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLD	ENST00000205402.10	c.118+2575A>G		intron_variant		1	NM_000108.5	ENSP00000205402.3

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100358 AN: 152024 Hom.: 33949 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.660 AC: 100473 AN: 152142 Hom.: 34002 Cov.: 32 AF XY: 0.664 AC XY: 49358 AN XY: 74370

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.637

Alfa AF: 0.621 Hom.: 4453

Bravo AF: 0.668

Asia WGS AF: 0.746 AC: 2596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.63

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: rs3801937; hg19: chr7-107536298;