rs4732038

Positions:

• chr7-134565570-A-C
• chr7-134565570-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080538.3(AKR1B15):​c.150+801A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,612,442 control chromosomes in the GnomAD database, including 213,468 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (20565 hom., cov: 32)
  • Exomes 𝑓: 0.51 (192903 hom.)
• Consequence: AKR1B15 NM_001080538.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1B15	NM_001080538.3	c.150+801A>C		intron_variant		ENST00000457545.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1B15	ENST00000457545.7	c.150+801A>C		intron_variant		5	NM_001080538.3
AKR1B15	ENST00000467156.1	n.759+24A>C		intron_variant, non_coding_transcript_variant		1
AKR1B15	ENST00000423958.2	c.150+801A>C		intron_variant		5
AKR1B15	ENST00000652743.1	c.66+24A>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78732 AN: 151816 Hom.: 20554 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.502

GnomAD3 exomes AF: 0.505 AC: 126101 AN: 249652 Hom.: 31937 AF XY: 0.502 AC XY: 67797 AN XY: 134930

Gnomad AFR exome AF: 0.574

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.466

Gnomad SAS exome AF: 0.480

Gnomad FIN exome AF: 0.468

Gnomad NFE exome AF: 0.518

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.513 AC: 748527 AN: 1460508 Hom.: 192903 Cov.: 53 AF XY: 0.511 AC XY: 371123 AN XY: 726512

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.509

GnomAD4 genome AF: 0.519 AC: 78781 AN: 151934 Hom.: 20565 Cov.: 32 AF XY: 0.514 AC XY: 38127 AN XY: 74238

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.503

Alfa AF: 0.509 Hom.: 10561

Bravo AF: 0.523

Asia WGS AF: 0.477 AC: 1657 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs4732038; hg19: chr7-134250322; COSMIC: COSV71152078;