10-4989823-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001393392.1(AKR1C2):c.*173G>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 0.0369 in 1,013,264 control chromosomes in the GnomAD database, including 1,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (543 hom., cov: 30)
  • Exomes 𝑓: 0.032 (639 hom.)
• Consequence: AKR1C2 NM_001393392.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.502

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 10-4989823-C-T is Benign according to our data. Variant chr10-4989823-C-T is described in ClinVar as [Benign]. Clinvar id is 1270279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1	c.*173G>A		3_prime_UTR_variant	9/9	ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9	c.*173G>A		3_prime_UTR_variant	9/9	1	NM_001393392.1	P1
AKR1C2	ENST00000421196.7	c.*173G>A		3_prime_UTR_variant	8/8	1
AKR1C2	ENST00000460124.5	n.2605G>A		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9748 AN: 151976 Hom.: 545 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.0321 AC: 27640 AN: 861170 Hom.: 639 Cov.: 12 AF XY: 0.0319 AC XY: 13987 AN XY: 437870

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.0245

Gnomad4 ASJ exome AF: 0.0521

Gnomad4 EAS exome AF: 0.00384

Gnomad4 SAS exome AF: 0.0269

Gnomad4 FIN exome AF: 0.0232

Gnomad4 NFE exome AF: 0.0305

Gnomad4 OTH exome AF: 0.0359

GnomAD4 genome AF: 0.0642 AC: 9765 AN: 152094 Hom.: 543 Cov.: 30 AF XY: 0.0614 AC XY: 4563 AN XY: 74356

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.00908

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.0481 Hom.: 44

Bravo AF: 0.0681

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.45
Dann	Benign	0.66

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: rs113349934; hg19: chr10-5032015;