chr10-4990242-C-A

Position:

• chr10-4990242-C-A

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.930-204G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,988 control chromosomes in the GnomAD database, including 15,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.44 (15733 hom., cov: 32)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36

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=-0.92).
• BP6: Variant 10-4990242-C-A is Benign according to our data. Variant chr10-4990242-C-A is described in ClinVar as [Benign]. Clinvar id is 1253500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1	c.930-204G>T		intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9	c.930-204G>T		intron_variant		1	NM_001393392.1	P1
AKR1C2	ENST00000421196.7	c.852-204G>T		intron_variant		1
AKR1C2	ENST00000460124.5	n.2390-204G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67190 AN: 151870 Hom.: 15728 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.442 AC: 67247 AN: 151988 Hom.: 15733 Cov.: 32 AF XY: 0.440 AC XY: 32657 AN XY: 74272

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.0619

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.414

Alfa AF: 0.473 Hom.: 2212

Bravo AF: 0.426

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	-0.92
CADD	Benign	1.2
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12355347; hg19: chr10-5032434;