rs5060

Variant names:

• chr7-134449726-C-T
• rs5060
• NM_001628.4:c.423G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-134449726-C-T
• chr7-134449726-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001346142.1(AKR1B1):​c.-10G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,613,900 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (37 hom.)
• Consequence: AKR1B1 NM_001346142.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.42
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-134449726-C-T is Benign according to our data. Variant chr7-134449726-C-T is described in ClinVar as Benign. ClinVar VariationId is 783507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0131 (1996/152290) while in subpopulation AFR AF = 0.0438 (1818/41546). AF 95% confidence interval is 0.0421. There are 47 homozygotes in GnomAd4. There are 960 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346142.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1B1	NM_001628.4	MANE Select	c.423G>A	p.Thr141Thr	synonymous	Exon 4 of 10	NP_001619.1	P15121
	AKR1B1	NM_001346142.1		c.-10G>A		5_prime_UTR_premature_start_codon_gain	Exon 4 of 10	NP_001333071.1
	AKR1B1	NM_001346142.1		c.-10G>A		5_prime_UTR	Exon 4 of 10	NP_001333071.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1B1	ENST00000285930.9	TSL:1 MANE Select	c.423G>A	p.Thr141Thr	synonymous	Exon 4 of 10	ENSP00000285930.3	P15121
	AKR1B1	ENST00000465351.5	TSL:1	n.463G>A		non_coding_transcript_exon	Exon 4 of 9
	AKR1B1	ENST00000467829.1	TSL:1	n.520G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1999 AN: 152172 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00387 AC: 973 AN: 251488 AF XY: 0.00291

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00152 AC: 2220 AN: 1461610 Hom.: 37 Cov.: 31 AF XY: 0.00133 AC XY: 966 AN XY: 727126

African (AFR) AF: 0.0432 AC: 1447 AN: 33470

American (AMR) AF: 0.00369 AC: 165 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00283 AC: 74 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.000285 AC: 317 AN: 1111752

Other (OTH) AF: 0.00333 AC: 201 AN: 60392

GnomAD4 genome AF: 0.0131 AC: 1996 AN: 152290 Hom.: 47 Cov.: 32 AF XY: 0.0129 AC XY: 960 AN XY: 74482

African (AFR) AF: 0.0438 AC: 1818 AN: 41546

American (AMR) AF: 0.00713 AC: 109 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68020

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00485 Hom.: 19

Bravo AF: 0.0147

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.27
DANN	Benign	0.77
PhyloP100		-6.4
Mutation Taster		=100/0	polymorphism

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: rs5060; hg19: chr7-134134478;