10-4990094-C-G

Position:

• chr10-4990094-C-G

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.930-56G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,599,732 control chromosomes in the GnomAD database, including 81,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7161 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74502 hom.)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.05

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=-1.01).
• BP6: Variant 10-4990094-C-G is Benign according to our data. Variant chr10-4990094-C-G is described in ClinVar as [Benign]. Clinvar id is 1262116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C2	NM_001393392.1	c.930-56G>C		intron_variant		ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C2	ENST00000380753.9	c.930-56G>C		intron_variant		1	NM_001393392.1	ENSP00000370129	P1
AKR1C2	ENST00000421196.7	c.852-56G>C		intron_variant		1		ENSP00000392694
AKR1C2	ENST00000460124.5	n.2390-56G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44081 AN: 151682 Hom.: 7161 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.307 AC: 444057 AN: 1447932 Hom.: 74502 AF XY: 0.313 AC XY: 225443 AN XY: 720526

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.623

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.290 AC: 44095 AN: 151800 Hom.: 7161 Cov.: 32 AF XY: 0.299 AC XY: 22189 AN XY: 74188

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.312

Alfa AF: 0.146 Hom.: 291

Bravo AF: 0.296

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	-1.0
CADD	Benign	0.14
DANN	Benign	0.40

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: rs4307630; hg19: chr10-5032286;