rs17188118

chr7-134457316-A-Cchr7-134457316-A-T

Variant summary

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

The NM_001628.4(AKR1B1):c.66+1681T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 152,250 control chromosomes in the GnomAD database, including 460 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 0.066 (460 hom., cov: 32)
• Consequence: AKR1B1 NM_001628.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385

Genes affected

AKR1B1 (HGNC:381): (aldo-keto reductase family 1 member B) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member catalyzes the reduction of a number of aldehydes, including the aldehyde form of glucose, and is thereby implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. Multiple pseudogenes have been identified for this gene. The nomenclature system used by the HUGO Gene Nomenclature Committee to define human aldo-keto reductase family members is known to differ from that used by the Mouse Genome Informatics database. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1B1	NM_001628.4	c.66+1681T>G		intron_variant		ENST00000285930.9
AKR1B1	NM_001346142.1	c.-367+1806T>G		intron_variant
AKR1B1	NR_144376.2	n.104+1681T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1B1	ENST00000285930.9	c.66+1681T>G		intron_variant		1	NM_001628.4	P1

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 10005 AN: 152132 Hom.: 461 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0704

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

GnomAD4 genome AF: 0.0657 AC: 10002 AN: 152250 Hom.: 460 Cov.: 32 AF XY: 0.0627 AC XY: 4668 AN XY: 74442

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0697

Alfa AF: 0.0744 Hom.: 70

Bravo AF: 0.0597

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	8.1
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs17188118; hg19: chr7-134142068;