7-134459206-G-A

Variant names:

• chr7-134459206-G-A
• rs759853
• ENST00000467829.1:n.79C>T

Variant summary

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

The ENST00000467829.1(AKR1B1):​n.79C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 979,370 control chromosomes in the GnomAD database, including 70,332 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 (8577 hom., cov: 33)
  • Exomes 𝑓: 0.38 (61755 hom.)
• Consequence: AKR1B1 ENST00000467829.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 81 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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.-451C>T		5_prime_UTR	Exon 1 of 10	NP_001333071.1
	AKR1B1	NM_001628.4	MANE Select	c.-144C>T		upstream_gene	N/A	NP_001619.1
	AKR1B1	NR_144376.2		n.-106C>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1B1	ENST00000467829.1	TSL:1	n.79C>T		non_coding_transcript_exon	Exon 1 of 4
	AKR1B1	ENST00000491741.5	TSL:1	n.79C>T		non_coding_transcript_exon	Exon 1 of 4
	AKR1B1	ENST00000497983.5	TSL:4	n.47C>T		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49260 AN: 149092 Hom.: 8573 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.243

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.384 AC: 318563 AN: 830154 Hom.: 61755 Cov.: 11 AF XY: 0.385 AC XY: 162169 AN XY: 421080

African (AFR) AF: 0.203 AC: 4187 AN: 20632

American (AMR) AF: 0.346 AC: 10844 AN: 31350

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 6998 AN: 20130

East Asian (EAS) AF: 0.188 AC: 6088 AN: 32326

South Asian (SAS) AF: 0.393 AC: 22482 AN: 57242

European-Finnish (FIN) AF: 0.357 AC: 12326 AN: 34504

Middle Eastern (MID) AF: 0.319 AC: 905 AN: 2838

European-Non Finnish (NFE) AF: 0.406 AC: 240788 AN: 592570

Other (OTH) AF: 0.362 AC: 13945 AN: 38562

GnomAD4 genome AF: 0.330 AC: 49286 AN: 149216 Hom.: 8577 Cov.: 33 AF XY: 0.327 AC XY: 23852 AN XY: 72876

African (AFR) AF: 0.210 AC: 8670 AN: 41220

American (AMR) AF: 0.329 AC: 4991 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1217 AN: 3432

East Asian (EAS) AF: 0.197 AC: 988 AN: 5026

South Asian (SAS) AF: 0.386 AC: 1646 AN: 4260

European-Finnish (FIN) AF: 0.342 AC: 3584 AN: 10466

Middle Eastern (MID) AF: 0.257 AC: 73 AN: 284

European-Non Finnish (NFE) AF: 0.408 AC: 27076 AN: 66374

Other (OTH) AF: 0.334 AC: 694 AN: 2078

Alfa AF: 0.357 Hom.: 12867

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.84
PhyloP100		-0.20
PromoterAI		0.072	Neutral

Splicing

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

Other links and lift over

dbSNP: rs759853; hg19: chr7-134143958; COSMIC: COSV53649543;