Variant 7-134448001-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001628.4(AKR1B1):c.720G>A(p.Lys240=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,613,026 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0076 ( 64 hom. )

Consequence

AKR1B1
NM_001628.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0400

Variant links:

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]

AKR1B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 7-134448001-C-T is Benign according to our data. Variant chr7-134448001-C-T is described in ClinVar as [Benign]. Clinvar id is 777632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.04 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKR1B1	NM_001628.4 linkuse as main transcript	c.720G>A	p.Lys240=	synonymous_variant	7/10	ENST00000285930.9
AKR1B1	NM_001346142.1 linkuse as main transcript	c.288G>A	p.Lys96=	synonymous_variant	7/10
AKR1B1	NR_144376.2 linkuse as main transcript	n.758G>A		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1B1	ENST00000285930.9 linkuse as main transcript	c.720G>A	p.Lys240=	synonymous_variant	7/10	1	NM_001628.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

805

AN:

151796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00217

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000628

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00787

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00552

AC:

1377

AN:

249624

Hom.:

AF XY:

0.00540

AC XY:

728

AN XY:

134766

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000962

Gnomad FIN exome

AF:

0.0145

Gnomad NFE exome

AF:

0.00814

Gnomad OTH exome

AF:

0.00494

GnomAD4 exome

AF:

0.00763

AC:

11145

AN:

1461112

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

5271

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000990

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.00886

Gnomad4 OTH exome

AF:

0.00638

GnomAD4 genome

AF:

0.00529

AC:

804

AN:

151914

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

379

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00217

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000629

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.00786

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00660

Hom.:

Bravo

AF:

0.00417

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00631

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

8.7

DANN

Benign

0.63

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over