rs1872929

Variant names:

• chr7-138116667-A-C
• rs1872929
• NM_005989.4:c.*5A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-138116667-A-C
• chr7-138116667-A-G
• chr7-138116667-A-T

Variant summary

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

The NM_005989.4(AKR1D1):​c.*5A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,613,284 control chromosomes in the GnomAD database, including 505,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49563 hom., cov: 32)
  • Exomes 𝑓: 0.79 (455771 hom.)
• Consequence: AKR1D1 NM_005989.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.358
• Publications: 15 publications found

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]

AKR1D1 Gene-Disease associations (from GenCC):

• congenital bile acid synthesis defect 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ENSG00000308006 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-138116667-A-C is Benign according to our data. Variant chr7-138116667-A-C is described in ClinVar as Benign. ClinVar VariationId is 259891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1D1	NM_005989.4	c.*5A>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000242375.8	NP_005980.1
AKR1D1	NM_001190907.2	c.*30A>C		3_prime_UTR_variant	Exon 8 of 8		NP_001177836.1
AKR1D1	NM_001190906.2	c.*5A>C		3_prime_UTR_variant	Exon 8 of 8		NP_001177835.1
AKR1D1	XM_047420763.1	c.*5A>C		3_prime_UTR_variant	Exon 8 of 8		XP_047276719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1D1	ENST00000242375.8	c.*5A>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_005989.4	ENSP00000242375.3

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122307 AN: 152014 Hom.: 49516 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.858

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.787

GnomAD2 exomes AF: 0.772 AC: 194140 AN: 251414 AF XY: 0.775

Gnomad AFR exome AF: 0.876

Gnomad AMR exome AF: 0.638

Gnomad ASJ exome AF: 0.784

Gnomad EAS exome AF: 0.738

Gnomad FIN exome AF: 0.818

Gnomad NFE exome AF: 0.795

Gnomad OTH exome AF: 0.779

GnomAD4 exome AF: 0.789 AC: 1152565 AN: 1461152 Hom.: 455771 Cov.: 43 AF XY: 0.789 AC XY: 573367 AN XY: 726914

African (AFR) AF: 0.879 AC: 29416 AN: 33472

American (AMR) AF: 0.641 AC: 28665 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 20379 AN: 26130

East Asian (EAS) AF: 0.741 AC: 29403 AN: 39696

South Asian (SAS) AF: 0.771 AC: 66490 AN: 86244

European-Finnish (FIN) AF: 0.815 AC: 43536 AN: 53388

Middle Eastern (MID) AF: 0.740 AC: 4269 AN: 5768

European-Non Finnish (NFE) AF: 0.794 AC: 882874 AN: 1111380

Other (OTH) AF: 0.788 AC: 47533 AN: 60358

GnomAD4 genome AF: 0.805 AC: 122410 AN: 152132 Hom.: 49563 Cov.: 32 AF XY: 0.802 AC XY: 59668 AN XY: 74386

African (AFR) AF: 0.877 AC: 36403 AN: 41500

American (AMR) AF: 0.678 AC: 10355 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2706 AN: 3472

East Asian (EAS) AF: 0.735 AC: 3793 AN: 5160

South Asian (SAS) AF: 0.772 AC: 3726 AN: 4824

European-Finnish (FIN) AF: 0.814 AC: 8615 AN: 10580

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54146 AN: 67998

Other (OTH) AF: 0.788 AC: 1668 AN: 2116

Alfa AF: 0.792 Hom.: 156961

Bravo AF: 0.795

Asia WGS AF: 0.772 AC: 2682 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 05, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital bile acid synthesis defect 2 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	2.7
DANN	Benign	0.59
PhyloP100		0.36
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: rs1872929; hg19: chr7-137801413;