rs4732038

Variant names:

• chr7-134565570-A-C
• rs4732038
• NM_001080538.3:c.150+801A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

ENSG00000298133 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080538.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1B15	NM_001080538.3	MANE Select	c.150+801A>C		intron	N/A	NP_001074007.2	C9JRZ8-2
	AKR1B15	NM_001367820.1		c.150+801A>C		intron	N/A	NP_001354749.1	C9JRZ8-2
	AKR1B15	NM_001367821.1		c.66+24A>C		intron	N/A	NP_001354750.1	C9JRZ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1B15	ENST00000457545.7	TSL:5 MANE Select	c.150+801A>C		intron	N/A	ENSP00000389289.1	C9JRZ8-2
	AKR1B15	ENST00000467156.1	TSL:1	n.759+24A>C		intron	N/A
	AKR1B15	ENST00000423958.2	TSL:5	c.150+801A>C		intron	N/A	ENSP00000397009.2	C9JRZ8-2

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

GnomAD2 exomes AF: 0.505 AC: 126101 AN: 249652 AF XY: 0.502

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 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

African (AFR) AF: 0.575 AC: 19245 AN: 33448

American (AMR) AF: 0.503 AC: 22415 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 12535 AN: 26108

East Asian (EAS) AF: 0.444 AC: 17566 AN: 39574

South Asian (SAS) AF: 0.484 AC: 41744 AN: 86200

European-Finnish (FIN) AF: 0.470 AC: 25068 AN: 53312

Middle Eastern (MID) AF: 0.441 AC: 2535 AN: 5754

European-Non Finnish (NFE) AF: 0.519 AC: 576680 AN: 1111170

Other (OTH) AF: 0.509 AC: 30739 AN: 60336

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

African (AFR) AF: 0.570 AC: 23610 AN: 41416

American (AMR) AF: 0.486 AC: 7423 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2362 AN: 5154

South Asian (SAS) AF: 0.469 AC: 2262 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4876 AN: 10532

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34998 AN: 67944

Other (OTH) AF: 0.503 AC: 1062 AN: 2112

Alfa AF: 0.511 Hom.: 15219

Bravo AF: 0.523

Asia WGS AF: 0.477 AC: 1657 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.45
PhyloP100		-0.92
PromoterAI		-0.072	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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