10-4989685-C-T

Variant names:

• chr10-4989685-C-T
• rs10904383
• NM_001393392.1:c.*311G>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.*311G>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 0.297 in 384,332 control chromosomes in the GnomAD database, including 19,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6939 hom., cov: 29)
  • Exomes 𝑓: 0.30 (12215 hom.)
• Consequence: AKR1C2 NM_001393392.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.128
• Publications: 2 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=-0.96).
• BP6: Variant 10-4989685-C-T is Benign according to our data. Variant chr10-4989685-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 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.*311G>A		3_prime_UTR	Exon 9 of 9	NP_001380321.1	P52895-1
	AKR1C2	NM_001354.6		c.*311G>A		3_prime_UTR	Exon 11 of 11	NP_001345.1	P52895-1
	AKR1C2	NM_205845.3		c.*311G>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.*311G>A		3_prime_UTR	Exon 9 of 9	ENSP00000370129.4	P52895-1
	AKR1C2	ENST00000421196.7	TSL:1	c.*311G>A		3_prime_UTR	Exon 8 of 8	ENSP00000392694.2	B4DK69
	AKR1C2	ENST00000867375.1		c.*311G>A		downstream_gene	N/A	ENSP00000537434.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43438 AN: 151558 Hom.: 6938 Cov.: 29

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.305 AC: 70865 AN: 232656 Hom.: 12215 Cov.: 2 AF XY: 0.314 AC XY: 38042 AN XY: 121056

African (AFR) AF: 0.190 AC: 1004 AN: 5278

American (AMR) AF: 0.397 AC: 1991 AN: 5010

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 2173 AN: 7750

East Asian (EAS) AF: 0.599 AC: 6885 AN: 11488

South Asian (SAS) AF: 0.470 AC: 10233 AN: 21756

European-Finnish (FIN) AF: 0.248 AC: 4998 AN: 20160

Middle Eastern (MID) AF: 0.333 AC: 371 AN: 1114

European-Non Finnish (NFE) AF: 0.267 AC: 38990 AN: 145916

Other (OTH) AF: 0.298 AC: 4220 AN: 14184

GnomAD4 genome AF: 0.286 AC: 43452 AN: 151676 Hom.: 6939 Cov.: 29 AF XY: 0.295 AC XY: 21868 AN XY: 74092

African (AFR) AF: 0.197 AC: 8133 AN: 41362

American (AMR) AF: 0.380 AC: 5795 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3466

East Asian (EAS) AF: 0.626 AC: 3227 AN: 5154

South Asian (SAS) AF: 0.510 AC: 2436 AN: 4772

European-Finnish (FIN) AF: 0.262 AC: 2751 AN: 10484

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19097 AN: 67894

Other (OTH) AF: 0.305 AC: 641 AN: 2102

Alfa AF: 0.301 Hom.: 1657

Bravo AF: 0.292

Asia WGS AF: 0.477 AC: 1658 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	-0.96
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		-0.13
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: rs10904383; hg19: chr10-5031877;