chr10-4826373-T-C

Variant names:

• chr10-4826373-T-C
• rs147185600
• NM_001040177.3:c.39+10T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040177.3(AKR1E2):​c.39+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,233,506 control chromosomes in the GnomAD database, including 2,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (254 hom., cov: 32)
  • Exomes 𝑓: 0.066 (2516 hom.)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.82
• Publications: 2 publications found

Genes affected

AKR1E2 (HGNC:23437): (aldo-keto reductase family 1 member E2) The protein encoded by this gene is a member of the aldo-keto reductase superfamily. Members in this family are characterized by their structure (evolutionarily highly conserved TIM barrel) and function (NAD(P)H-dependent oxido-reduction of carbonyl groups). Transcripts of this gene have been reported in specimens of human testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

AKR1E2 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-4826373-T-C is Benign according to our data. Variant chr10-4826373-T-C is described in ClinVar as Benign. ClinVar VariationId is 1246064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040177.3. 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
	AKR1E2	NM_001040177.3	MANE Select	c.39+10T>C		intron	N/A	NP_001035267.1	Q96JD6-1
	AKR1E2	NM_001271021.2		c.39+10T>C		intron	N/A	NP_001257950.1	Q96JD6-2
	AKR1E2	NM_001271025.2		c.39+10T>C		intron	N/A	NP_001257954.1	Q96JD6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	ENST00000298375.12	TSL:1 MANE Select	c.39+10T>C		intron	N/A	ENSP00000298375.7	Q96JD6-1
	AKR1E2	ENST00000334019.4	TSL:1	c.39+10T>C		intron	N/A	ENSP00000335034.4	Q96JD6-2
	AKR1E2	ENST00000532248.5	TSL:1	c.39+10T>C		intron	N/A	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7838 AN: 151858 Hom.: 254 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0243

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.0450

GnomAD2 exomes AF: 0.0553 AC: 181 AN: 3274 AF XY: 0.0521

Gnomad AFR exome AF: 0.0307

Gnomad AMR exome AF: 0.0357

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0699

Gnomad NFE exome AF: 0.0493

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0661 AC: 71512 AN: 1081540 Hom.: 2516 Cov.: 32 AF XY: 0.0658 AC XY: 33625 AN XY: 510908

African (AFR) AF: 0.0377 AC: 861 AN: 22866

American (AMR) AF: 0.0287 AC: 240 AN: 8368

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 572 AN: 14312

East Asian (EAS) AF: 0.0000756 AC: 2 AN: 26468

South Asian (SAS) AF: 0.0261 AC: 509 AN: 19492

European-Finnish (FIN) AF: 0.0883 AC: 2150 AN: 24348

Middle Eastern (MID) AF: 0.0309 AC: 92 AN: 2974

European-Non Finnish (NFE) AF: 0.0704 AC: 64673 AN: 919126

Other (OTH) AF: 0.0554 AC: 2413 AN: 43586

GnomAD4 genome AF: 0.0516 AC: 7842 AN: 151966 Hom.: 254 Cov.: 32 AF XY: 0.0506 AC XY: 3759 AN XY: 74278

African (AFR) AF: 0.0328 AC: 1361 AN: 41432

American (AMR) AF: 0.0307 AC: 469 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 138 AN: 3472

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5138

South Asian (SAS) AF: 0.0243 AC: 117 AN: 4808

European-Finnish (FIN) AF: 0.0813 AC: 860 AN: 10574

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0683 AC: 4639 AN: 67936

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0591 Hom.: 40

Bravo AF: 0.0482

Asia WGS AF: 0.0140 AC: 49 AN: 3470

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	-0.82
CADD	Benign	1.9
DANN	Benign	0.19
PhyloP100		-2.8
PromoterAI		0.032	Neutral
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: rs147185600; hg19: chr10-4868565;