Variant chr7-134568314-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001080538.3(AKR1B15):c.307A>G(p.Ile103Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

AKR1B15
NM_001080538.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.316

Variant links:

Genes affected

AKR1B15 (HGNC:37281): (aldo-keto reductase family 1 member B15) Enables estradiol 17-beta-dehydrogenase activity. Predicted to be involved in estrogen biosynthetic process. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

AKR1B15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005969465).

BP6

Variant 7-134568314-A-G is Benign according to our data. Variant chr7-134568314-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 717221.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1B15	NM_001080538.3 linkuse as main transcript	c.307A>G	p.Ile103Val	missense_variant	4/12	ENST00000457545.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1B15	ENST00000457545.7 linkuse as main transcript	c.307A>G	p.Ile103Val	missense_variant	4/12	5	NM_001080538.3		C9JRZ8-2
AKR1B15	ENST00000467156.1 linkuse as main transcript	n.916A>G		non_coding_transcript_exon_variant	2/3	1
AKR1B15	ENST00000423958.2 linkuse as main transcript	c.307A>G	p.Ile103Val	missense_variant	2/10	5			C9JRZ8-2
AKR1B15	ENST00000652743.1 linkuse as main transcript	c.223A>G	p.Ile75Val	missense_variant	2/10			P1	C9JRZ8-1

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000374

AC:

AN:

251268

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00535

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000140

AC:

204

AN:

1461782

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00544

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.00150

AC:

229

AN:

152324

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00536

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000319

Hom.:

Bravo

AF:

0.00141

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000511

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 11, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.92

.;D

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.82

L;L

MutationTaster

Benign

0.69

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.58

N;.

REVEL

Benign

0.029

Sift

Benign

0.40

T;.

Sift4G

Benign

0.35

T;T

Vest4

0.17

MVP

0.13

MPC

0.048

ClinPred

0.0029

GERP RS

1.6

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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