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7-134449726-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001628.4(AKR1B1):c.423G>A(p.Thr141=) variant causes a synonymous 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_001628.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.42
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 -15 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=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-134449726-C-T is Benign according to our data. Variant chr7-134449726-C-T is described in ClinVar as [Benign]. Clinvar id is 783507.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=-6.42 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
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 46 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKR1B1NM_001628.4 linkuse as main transcriptc.423G>A p.Thr141= synonymous_variant 4/10 ENST00000285930.9
AKR1B1NM_001346142.1 linkuse as main transcriptc.-10G>A 5_prime_UTR_variant 4/10
AKR1B1NR_144376.2 linkuse as main transcriptn.461G>A non_coding_transcript_exon_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKR1B1ENST00000285930.9 linkuse as main transcriptc.423G>A p.Thr141= synonymous_variant 4/101 NM_001628.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0131
AC:
1999
AN:
152172
Hom.:
46
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00387
AC:
973
AN:
251488
Hom.:
24
AF XY:
0.00291
AC XY:
396
AN XY:
135916
show subpopulations
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 SAS exome
AF:
0.0000653
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0432
Gnomad4 AMR exome
AF:
0.00369
Gnomad4 ASJ exome
AF:
0.00283
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000285
Gnomad4 OTH exome
AF:
0.00333
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0131
AC:
1996
AN:
152290
Hom.:
47
Cov.:
32
AF XY:
0.0129
AC XY:
960
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0438
Gnomad4 AMR
AF:
0.00713
Gnomad4 ASJ
AF:
0.00461
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.00946
Alfa
AF:
0.00424
Hom.:
14
Bravo
AF:
0.0147
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000356

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
-0.82
Cadd
Benign
0.27
Dann
Benign
0.77

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: rs5060; hg19: chr7-134134478; API