Variant chr7-134449714-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001628.4(AKR1B1):c.429+6A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,613,394 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 61 hom. )

Consequence

AKR1B1
NM_001628.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.00009719

Clinical Significance

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

Conservation

PhyloP100: -1.82

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-134449714-T-C is Benign according to our data. Variant chr7-134449714-T-C is described in ClinVar as [Benign]. Clinvar id is 770191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00474 (6925/1461142) while in subpopulation AMR AF= 0.0185 (827/44724). AF 95% confidence interval is 0.0174. There are 61 homozygotes in gnomad4_exome. There are 3426 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
AKR1B1	NM_001628.4 linkuse as main transcript	c.429+6A>G	splice_donor_region_variant, intron_variant	ENST00000285930.9	NP_001619.1
AKR1B1	NM_001346142.1 linkuse as main transcript	c.-4+6A>G	splice_donor_region_variant, intron_variant		NP_001333071.1
AKR1B1	NR_144376.2 linkuse as main transcript	n.467+6A>G	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1B1	ENST00000285930.9 linkuse as main transcript	c.429+6A>G		splice_donor_region_variant, intron_variant		1	NM_001628.4	ENSP00000285930	P1

Frequencies

GnomAD3 genomes

AF:

0.00578

AC:

879

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00754

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00419

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00877

AC:

2206

AN:

251466

Hom.:

AF XY:

0.00814

AC XY:

1106

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.0160

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.0305

Gnomad NFE exome

AF:

0.00402

Gnomad OTH exome

AF:

0.00863

GnomAD4 exome

AF:

0.00474

AC:

6925

AN:

1461142

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

3426

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.0185

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00388

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.00300

Gnomad4 OTH exome

AF:

0.00522

GnomAD4 genome

AF:

0.00580

AC:

883

AN:

152252

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

497

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00772

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0328

Gnomad4 NFE

AF:

0.00419

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00578

Hom.:

Bravo

AF:

0.00397

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00273

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

-0.80

CADD

Benign

3.9

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000097

dbscSNV1_RF

Benign

0.0040

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