15-45060867-G-A

Position:

• chr15-45060867-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003104.6(SORD):​c.266-200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 1,157,446 control chromosomes in the GnomAD database, including 2,882 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (382 hom., cov: 32)
  • Exomes 𝑓: 0.077 (2500 hom.)
• Consequence: SORD NM_003104.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0360

Genes affected

SORD (HGNC:11184): (sorbitol dehydrogenase) Sorbitol dehydrogenase (SORD; EC 1.1.1.14) catalyzes the interconversion of polyols and their corresponding ketoses, and together with aldose reductase (ALDR1; MIM 103880), makes up the sorbitol pathway that is believed to play an important role in the development of diabetic complications (summarized by Carr and Markham, 1995 [PubMed 8535074]). The first reaction of the pathway (also called the polyol pathway) is the reduction of glucose to sorbitol by ALDR1 with NADPH as the cofactor. SORD then oxidizes the sorbitol to fructose using NAD(+) cofactor.[supplied by OMIM, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-45060867-G-A is Benign according to our data. Variant chr15-45060867-G-A is described in ClinVar as [Benign]. Clinvar id is 1239849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORD	NM_003104.6	c.266-200G>A		intron_variant		ENST00000267814.14
SORD	NR_034039.2	n.355-115G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORD	ENST00000267814.14	c.266-200G>A		intron_variant		1	NM_003104.6	P1

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 9577 AN: 142594 Hom.: 376 Cov.: 32

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0377

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.0583

GnomAD4 exome AF: 0.0772 AC: 78322 AN: 1014754 Hom.: 2500 AF XY: 0.0787 AC XY: 39516 AN XY: 502180

Gnomad4 AFR exome AF: 0.0395

Gnomad4 AMR exome AF: 0.0320

Gnomad4 ASJ exome AF: 0.0553

Gnomad4 EAS exome AF: 0.0395

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.0784

Gnomad4 OTH exome AF: 0.0760

GnomAD4 genome AF: 0.0673 AC: 9600 AN: 142692 Hom.: 382 Cov.: 32 AF XY: 0.0686 AC XY: 4796 AN XY: 69868

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.0342

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.0660

Alfa AF: 0.0799 Hom.: 56

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs71480278; hg19: chr15-45353065;