chr10-4989699-G-T

Variant names:

• chr10-4989699-G-T
• rs113361610
• NM_001393392.1:c.*297C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001393392.1(AKR1C2):​c.*297C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 460,174 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (75 hom., cov: 30)
  • Exomes 𝑓: 0.0018 (14 hom.)
• Consequence: AKR1C2 NM_001393392.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.07
• Publications: 0 publications found

Genes affected

AKR1C2 (HGNC:385): (aldo-keto reductase family 1 member C2) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme binds bile acid with high affinity, and shows minimal 3-alpha-hydroxysteroid dehydrogenase activity. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AKR1C2 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to testicular 17,20-desmolase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-4989699-G-T is Benign according to our data. Variant chr10-4989699-G-T is described in ClinVar as Benign. ClinVar VariationId is 1250861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393392.1. 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
	AKR1C2	NM_001393392.1	MANE Select	c.*297C>A		3_prime_UTR	Exon 9 of 9	NP_001380321.1	P52895-1
	AKR1C2	NM_001354.6		c.*297C>A		3_prime_UTR	Exon 11 of 11	NP_001345.1	P52895-1
	AKR1C2	NM_205845.3		c.*297C>A		3_prime_UTR	Exon 10 of 10	NP_995317.1	P52895-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C2	ENST00000380753.9	TSL:1 MANE Select	c.*297C>A		3_prime_UTR	Exon 9 of 9	ENSP00000370129.4	P52895-1
	AKR1C2	ENST00000421196.7	TSL:1	c.*297C>A		3_prime_UTR	Exon 8 of 8	ENSP00000392694.2	B4DK69
	AKR1C2	ENST00000867375.1		c.*297C>A		downstream_gene	N/A	ENSP00000537434.1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2474 AN: 152044 Hom.: 73 Cov.: 30

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0138

GnomAD4 exome AF: 0.00179 AC: 552 AN: 308012 Hom.: 14 Cov.: 3 AF XY: 0.00160 AC XY: 259 AN XY: 161626

African (AFR) AF: 0.0604 AC: 418 AN: 6926

American (AMR) AF: 0.00440 AC: 33 AN: 7496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9762

East Asian (EAS) AF: 0.00 AC: 0 AN: 16676

South Asian (SAS) AF: 0.00 AC: 0 AN: 29290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28672

Middle Eastern (MID) AF: 0.00215 AC: 3 AN: 1398

European-Non Finnish (NFE) AF: 0.0000896 AC: 17 AN: 189688

Other (OTH) AF: 0.00447 AC: 81 AN: 18104

GnomAD4 genome AF: 0.0163 AC: 2487 AN: 152162 Hom.: 75 Cov.: 30 AF XY: 0.0156 AC XY: 1164 AN XY: 74398

African (AFR) AF: 0.0572 AC: 2371 AN: 41466

American (AMR) AF: 0.00491 AC: 75 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68020

Other (OTH) AF: 0.0137 AC: 29 AN: 2116

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.0183

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.035
DANN	Benign	0.51
PhyloP100		-2.1
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: rs113361610; hg19: chr10-5031891;