10-4847211-C-T

Variant names:

• chr10-4847211-C-T
• rs12240276
• NM_001040177.3:c.901C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001040177.3(AKR1E2):​c.901C>T​(p.Arg301*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,613,686 control chromosomes in the GnomAD database, including 10,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (901 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9111 hom.)
• Consequence: AKR1E2 NM_001040177.3 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.86
• Publications: 31 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 -16 ACMG points.

• BP6: Variant 10-4847211-C-T is Benign according to our data. Variant chr10-4847211-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1E2	NM_001040177.3	c.901C>T	p.Arg301*	stop_gained	Exon 9 of 10	ENST00000298375.12	NP_001035267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1E2	ENST00000298375.12	c.901C>T	p.Arg301*	stop_gained	Exon 9 of 10	1	NM_001040177.3	ENSP00000298375.7

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15644 AN: 152038 Hom.: 902 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0779

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0948 AC: 23820 AN: 251340 AF XY: 0.0959

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.0739

Gnomad ASJ exome AF: 0.0841

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.0989

GnomAD4 exome AF: 0.108 AC: 158062 AN: 1461530 Hom.: 9111 Cov.: 32 AF XY: 0.108 AC XY: 78267 AN XY: 727064

African (AFR) AF: 0.0978 AC: 3274 AN: 33460

American (AMR) AF: 0.0734 AC: 3281 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 2233 AN: 26132

East Asian (EAS) AF: 0.000680 AC: 27 AN: 39692

South Asian (SAS) AF: 0.0775 AC: 6681 AN: 86224

European-Finnish (FIN) AF: 0.113 AC: 6040 AN: 53404

Middle Eastern (MID) AF: 0.105 AC: 607 AN: 5766

European-Non Finnish (NFE) AF: 0.117 AC: 129715 AN: 1111778

Other (OTH) AF: 0.103 AC: 6204 AN: 60378

GnomAD4 genome AF: 0.103 AC: 15649 AN: 152156 Hom.: 901 Cov.: 33 AF XY: 0.102 AC XY: 7556 AN XY: 74388

African (AFR) AF: 0.0998 AC: 4143 AN: 41500

American (AMR) AF: 0.0727 AC: 1111 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0784 AC: 378 AN: 4820

European-Finnish (FIN) AF: 0.113 AC: 1198 AN: 10578

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8189 AN: 67998

Other (OTH) AF: 0.0991 AC: 209 AN: 2110

Alfa AF: 0.109 Hom.: 3141

Bravo AF: 0.0983

TwinsUK AF: 0.111 AC: 413

ALSPAC AF: 0.114 AC: 438

ESP6500AA AF: 0.0990 AC: 436

ESP6500EA AF: 0.115 AC: 990

ExAC AF: 0.0968 AC: 11754

EpiCase AF: 0.118

EpiControl AF: 0.114

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27535653) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	42
DANN	Uncertain	0.98
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.47	N
PhyloP100		1.9
Vest4		0.12
GERP RS		4.5
Mutation Taster		=123/77	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.28		Position offset: 19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12240276; hg19: chr10-4889403; COSMIC: COSV53632137; COSMIC: COSV53632137;