chr7-134459206-G-T

Variant names:

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

Variant summary

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

The ENST00000467829.1(AKR1B1):​n.79C>A 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 0.0000012 in 831,652 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: 33)
  • Exomes 𝑓: 0.0000012 (0 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: 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=-0.85).

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>A		5_prime_UTR	Exon 1 of 10	NP_001333071.1
	AKR1B1	NM_001628.4	MANE Select	c.-144C>A		upstream_gene	N/A	NP_001619.1
	AKR1B1	NR_144376.2		n.-106C>A		upstream_gene	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 831652 Hom.: 0 Cov.: 11 AF XY: 0.00000237 AC XY: 1 AN XY: 421826

African (AFR) AF: 0.00 AC: 0 AN: 20664

American (AMR) AF: 0.00 AC: 0 AN: 31370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20164

East Asian (EAS) AF: 0.00 AC: 0 AN: 32336

South Asian (SAS) AF: 0.0000175 AC: 1 AN: 57304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2838

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 593824

Other (OTH) AF: 0.00 AC: 0 AN: 38620

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 12867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.70
PhyloP100		-0.20
PromoterAI		0.030	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;