rs1872930

Positions:

• chr7-138116698-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005989.4(AKR1D1):​c.*36C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,605,206 control chromosomes in the GnomAD database, including 499,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48947 hom., cov: 32)
  • Exomes 𝑓: 0.79 (450686 hom.)
• Consequence: AKR1D1 NM_005989.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.67

Genes affected

AKR1D1 (HGNC:388): (aldo-keto reductase family 1 member D1) The enzyme encoded by this gene is responsible for the catalysis of the 5-beta-reduction of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure. Deficiency of this enzyme may contribute to hepatic dysfunction. Three transcript variants encoding different isoforms have been found for this gene. Other variants may be present, but their full-length natures have not been determined yet. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-138116698-C-T is Benign according to our data. Variant chr7-138116698-C-T is described in ClinVar as [Benign]. Clinvar id is 358956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1D1	NM_005989.4	c.*36C>T		3_prime_UTR_variant	9/9	ENST00000242375.8	NP_005980.1
AKR1D1	NM_001190906.2	c.*36C>T		3_prime_UTR_variant	8/8		NP_001177835.1
AKR1D1	NM_001190907.2	c.*61C>T		3_prime_UTR_variant	8/8		NP_001177836.1
AKR1D1	XM_047420763.1	c.*36C>T		3_prime_UTR_variant	8/8		XP_047276719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1D1	ENST00000242375.8	c.*36C>T		3_prime_UTR_variant	9/9	1	NM_005989.4	ENSP00000242375	P1
AKR1D1	ENST00000411726.6	c.*36C>T		3_prime_UTR_variant	8/8	2		ENSP00000402374
AKR1D1	ENST00000432161.5	c.*61C>T		3_prime_UTR_variant	8/8	2		ENSP00000389197
AKR1D1	ENST00000468877.2	n.1040C>T		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121584 AN: 152038 Hom.: 48909 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.785

GnomAD3 exomes AF: 0.769 AC: 193283 AN: 251182 Hom.: 74951 AF XY: 0.772 AC XY: 104855 AN XY: 135776

Gnomad AFR exome AF: 0.867

Gnomad AMR exome AF: 0.637

Gnomad ASJ exome AF: 0.784

Gnomad EAS exome AF: 0.738

Gnomad SAS exome AF: 0.767

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.792

Gnomad OTH exome AF: 0.778

GnomAD4 exome AF: 0.787 AC: 1142884 AN: 1453050 Hom.: 450686 Cov.: 29 AF XY: 0.787 AC XY: 568989 AN XY: 723408

Gnomad4 AFR exome AF: 0.868

Gnomad4 AMR exome AF: 0.640

Gnomad4 ASJ exome AF: 0.780

Gnomad4 EAS exome AF: 0.740

Gnomad4 SAS exome AF: 0.770

Gnomad4 FIN exome AF: 0.806

Gnomad4 NFE exome AF: 0.793

Gnomad4 OTH exome AF: 0.785

GnomAD4 genome AF: 0.800 AC: 121677 AN: 152156 Hom.: 48947 Cov.: 32 AF XY: 0.797 AC XY: 59307 AN XY: 74400

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.786

Alfa AF: 0.783 Hom.: 46971

Bravo AF: 0.790

Asia WGS AF: 0.768 AC: 2668 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Nov 10, 2018	This variant is associated with the following publications: (PMID: 23704699) -

Congenital bile acid synthesis defect 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.032
DANN	Benign	0.63

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: rs1872930; hg19: chr7-137801444;