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GeneBe

7-134448001-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.04 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKR1B1NM_001628.4 linkuse as main transcriptc.720G>A p.Lys240= synonymous_variant 7/10 ENST00000285930.9
AKR1B1NM_001346142.1 linkuse as main transcriptc.288G>A p.Lys96= synonymous_variant 7/10
AKR1B1NR_144376.2 linkuse as main transcriptn.758G>A non_coding_transcript_exon_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKR1B1ENST00000285930.9 linkuse as main transcriptc.720G>A p.Lys240= synonymous_variant 7/101 NM_001628.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00530
AC:
805
AN:
151796
Hom.:
4
Cov.:
31
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.:
10
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.:
64
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00529
AC:
804
AN:
151914
Hom.:
4
Cov.:
31
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.:
1
Bravo
AF:
0.00417
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00703
EpiControl
AF:
0.00631

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs114023160; hg19: chr7-134132753; COSMIC: COSV99605325; COSMIC: COSV99605325; API