rs5053

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-134459111-G-A
• chr7-134459111-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000467829.1(AKR1B1):​n.163+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1B1	NM_001346142.1	c.-367+11C>T		intron_variant	Intron 1 of 9		NP_001333071.1
AKR1B1	NM_001628.4	c.-49C>T		upstream_gene_variant		ENST00000285930.9	NP_001619.1
AKR1B1	NR_144376.2	n.-11C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1B1	ENST00000285930.9	c.-49C>T		upstream_gene_variant		1	NM_001628.4	ENSP00000285930.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417796 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701414

African (AFR) AF: 0.00 AC: 0 AN: 32400

American (AMR) AF: 0.00 AC: 0 AN: 38554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25314

East Asian (EAS) AF: 0.00 AC: 0 AN: 37292

South Asian (SAS) AF: 0.00 AC: 0 AN: 80668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089420

Other (OTH) AF: 0.00 AC: 0 AN: 58732

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 85

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		-1.5
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

Other links and lift over

dbSNP: rs5053; hg19: chr7-134143863;