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GeneBe

7-134450843-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001628.4(AKR1B1):c.294C>T(p.Ser98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000841 in 1,614,168 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 6 hom. )

Consequence

AKR1B1
NM_001628.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.34
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 -11 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=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-134450843-G-A is Benign according to our data. Variant chr7-134450843-G-A is described in ClinVar as [Benign]. Clinvar id is 712685.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=-3.34 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 GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKR1B1NM_001628.4 linkuse as main transcriptc.294C>T p.Ser98= synonymous_variant 3/10 ENST00000285930.9
AKR1B1NM_001346142.1 linkuse as main transcriptc.-139C>T 5_prime_UTR_variant 3/10
AKR1B1NR_144376.2 linkuse as main transcriptn.332C>T non_coding_transcript_exon_variant 3/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKR1B1ENST00000285930.9 linkuse as main transcriptc.294C>T p.Ser98= synonymous_variant 3/101 NM_001628.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00416
AC:
633
AN:
152212
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0146
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00119
AC:
300
AN:
251420
Hom.:
2
AF XY:
0.000854
AC XY:
116
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.0159
Gnomad AMR exome
AF:
0.000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000703
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.000495
AC:
723
AN:
1461838
Hom.:
6
Cov.:
32
AF XY:
0.000402
AC XY:
292
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0157
Gnomad4 AMR exome
AF:
0.000760
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000890
Gnomad4 OTH exome
AF:
0.000745
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00416
AC:
634
AN:
152330
Hom.:
1
Cov.:
32
AF XY:
0.00428
AC XY:
319
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0146
Gnomad4 AMR
AF:
0.000915
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00233
Hom.:
0
Bravo
AF:
0.00483
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

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
-0.65
Cadd
Benign
0.97
Dann
Benign
0.58
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs116793843; hg19: chr7-134135595; API