7-134459111-G-C

Variant names:

• chr7-134459111-G-C
• rs5053
• ENST00000467829.1:n.163+11C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000467829.1(AKR1B1):​n.163+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 1,569,884 control chromosomes in the GnomAD database, including 8,873 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 0.15 (3863 hom., cov: 34)
  • Exomes 𝑓: 0.050 (5010 hom.)
• Consequence: AKR1B1 ENST00000467829.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000467829.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1B1	NM_001346142.1		c.-367+11C>G		intron	N/A	NP_001333071.1
	AKR1B1	NM_001628.4	MANE Select	c.-49C>G		upstream_gene	N/A	NP_001619.1
	AKR1B1	NR_144376.2		n.-11C>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1B1	ENST00000467829.1	TSL:1	n.163+11C>G		intron	N/A
	AKR1B1	ENST00000491741.5	TSL:1	n.163+11C>G		intron	N/A
	AKR1B1	ENST00000462784.1	TSL:2	n.24C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22823 AN: 152092 Hom.: 3850 Cov.: 34

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.135

GnomAD2 exomes AF: 0.0767 AC: 13667 AN: 178124 AF XY: 0.0689

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.0583

Gnomad ASJ exome AF: 0.0289

Gnomad EAS exome AF: 0.215

Gnomad FIN exome AF: 0.0228

Gnomad NFE exome AF: 0.0315

Gnomad OTH exome AF: 0.0654

GnomAD4 exome AF: 0.0500 AC: 70914 AN: 1417674 Hom.: 5010 Cov.: 31 AF XY: 0.0493 AC XY: 34566 AN XY: 701360

African (AFR) AF: 0.425 AC: 13753 AN: 32384

American (AMR) AF: 0.0605 AC: 2331 AN: 38552

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 715 AN: 25314

East Asian (EAS) AF: 0.214 AC: 7968 AN: 37286

South Asian (SAS) AF: 0.0688 AC: 5550 AN: 80660

European-Finnish (FIN) AF: 0.0224 AC: 1116 AN: 49848

Middle Eastern (MID) AF: 0.0805 AC: 447 AN: 5552

European-Non Finnish (NFE) AF: 0.0319 AC: 34742 AN: 1089348

Other (OTH) AF: 0.0731 AC: 4292 AN: 58730

GnomAD4 genome AF: 0.150 AC: 22875 AN: 152210 Hom.: 3863 Cov.: 34 AF XY: 0.147 AC XY: 10941 AN XY: 74432

African (AFR) AF: 0.419 AC: 17416 AN: 41524

American (AMR) AF: 0.0729 AC: 1115 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1137 AN: 5146

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4822

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10612

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0323 AC: 2199 AN: 68016

Other (OTH) AF: 0.138 AC: 291 AN: 2114

Alfa AF: 0.0356 Hom.: 85

Bravo AF: 0.167

Asia WGS AF: 0.171 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.83
DANN	Benign	0.49
PhyloP100		-1.5
PromoterAI		-0.064	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs5053; hg19: chr7-134143863; COSMIC: COSV53646746; COSMIC: COSV53646746;