rs748600907

Variant names:

• chr7-134575510-C-A
• rs748600907
• NM_001080538.3:c.604C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-134575510-C-A
• chr7-134575510-C-G
• chr7-134575510-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080538.3(AKR1B15):​c.604C>A​(p.Pro202Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P202A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AKR1B15 NM_001080538.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.70

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1B15	NM_001080538.3	c.604C>A	p.Pro202Thr	missense_variant	Exon 7 of 12	ENST00000457545.7	NP_001074007.2
AKR1B15	NM_001367820.1	c.604C>A	p.Pro202Thr	missense_variant	Exon 6 of 11		NP_001354749.1
AKR1B15	NM_001367821.1	c.520C>A	p.Pro174Thr	missense_variant	Exon 6 of 11		NP_001354750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1B15	ENST00000457545.7	c.604C>A	p.Pro202Thr	missense_variant	Exon 7 of 12	5	NM_001080538.3	ENSP00000389289.1
AKR1B15	ENST00000423958.2	c.604C>A	p.Pro202Thr	missense_variant	Exon 5 of 10	5		ENSP00000397009.2
AKR1B15	ENST00000652743.1	c.520C>A	p.Pro174Thr	missense_variant	Exon 5 of 10			ENSP00000498877.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461584 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727100

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111786

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.10	N;N
PhyloP100		5.7
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.7	D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.015	D;D
Vest4		0.66
MutPred		0.70		Loss of methylation at K205 (P = 0.1);Loss of methylation at K205 (P = 0.1);
MVP		0.24
MPC		0.30
ClinPred		0.94	D
GERP RS		3.8
gMVP		0.14
Mutation Taster		=93/7	polymorphism

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

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Other links and lift over

dbSNP: rs748600907; hg19: chr7-134260262;