7-134452953-C-T

Position:

• chr7-134452953-C-T

Variant summary

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

The NM_001628.4(AKR1B1):​c.67-1200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,984 control chromosomes in the GnomAD database, including 8,993 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 0.33 (8993 hom., cov: 32)
• Consequence: AKR1B1 NM_001628.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1B1	NM_001628.4	c.67-1200G>A		intron_variant		ENST00000285930.9	NP_001619.1
AKR1B1	NM_001346142.1	c.-366-1200G>A		intron_variant			NP_001333071.1
AKR1B1	NR_144376.2	n.105-1200G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1B1	ENST00000285930.9	c.67-1200G>A		intron_variant		1	NM_001628.4	ENSP00000285930	P1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50565 AN: 151866 Hom.: 8986 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.333 AC: 50581 AN: 151984 Hom.: 8993 Cov.: 32 AF XY: 0.328 AC XY: 24369 AN XY: 74262

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.334

Alfa AF: 0.387 Hom.: 19330

Bravo AF: 0.329

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.25
DANN	Benign	0.77

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: rs3896278; hg19: chr7-134137705;