10-4989685-C-T

Position:

• chr10-4989685-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C2	NM_001393392.1	c.*311G>A		3_prime_UTR_variant	9/9	ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C2	ENST00000380753.9	c.*311G>A		3_prime_UTR_variant	9/9	1	NM_001393392.1	ENSP00000370129	P1
AKR1C2	ENST00000421196.7	c.*311G>A		3_prime_UTR_variant	8/8	1		ENSP00000392694

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

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.599

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.298

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

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.305

Alfa AF: 0.307 Hom.: 1498

Bravo AF: 0.292

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.57

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: rs10904383; hg19: chr10-5031877;