rs1872930

Variant names:

• chr7-138116698-C-T
• rs1872930
• NM_005989.4:c.*36C>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.*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
• Publications: 21 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), 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 7-138116698-C-T is Benign according to our data. Variant chr7-138116698-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005989.4. 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
	AKR1D1	NM_005989.4	MANE Select	c.*36C>T		3_prime_UTR	Exon 9 of 9	NP_005980.1	P51857-1
	AKR1D1	NM_001190907.2		c.*61C>T		3_prime_UTR	Exon 8 of 8	NP_001177836.1	P51857-2
	AKR1D1	NM_001190906.2		c.*36C>T		3_prime_UTR	Exon 8 of 8	NP_001177835.1	P51857-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1D1	ENST00000242375.8	TSL:1 MANE Select	c.*36C>T		3_prime_UTR	Exon 9 of 9	ENSP00000242375.3	P51857-1
	AKR1D1	ENST00000885436.1		c.*36C>T		3_prime_UTR	Exon 11 of 11	ENSP00000555495.1
	AKR1D1	ENST00000885435.1		c.*36C>T		3_prime_UTR	Exon 10 of 10	ENSP00000555494.1

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

GnomAD2 exomes AF: 0.769 AC: 193283 AN: 251182 AF XY: 0.772

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 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

African (AFR) AF: 0.868 AC: 28930 AN: 33322

American (AMR) AF: 0.640 AC: 28602 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 20333 AN: 26076

East Asian (EAS) AF: 0.740 AC: 29347 AN: 39652

South Asian (SAS) AF: 0.770 AC: 66288 AN: 86102

European-Finnish (FIN) AF: 0.806 AC: 42872 AN: 53224

Middle Eastern (MID) AF: 0.738 AC: 4243 AN: 5750

European-Non Finnish (NFE) AF: 0.793 AC: 875087 AN: 1104120

Other (OTH) AF: 0.785 AC: 47182 AN: 60100

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

African (AFR) AF: 0.866 AC: 35955 AN: 41528

American (AMR) AF: 0.677 AC: 10337 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2707 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3793 AN: 5168

South Asian (SAS) AF: 0.774 AC: 3729 AN: 4820

European-Finnish (FIN) AF: 0.803 AC: 8495 AN: 10576

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

European-Non Finnish (NFE) AF: 0.794 AC: 54004 AN: 68004

Other (OTH) AF: 0.786 AC: 1657 AN: 2108

Alfa AF: 0.784 Hom.: 60891

Bravo AF: 0.790

Asia WGS AF: 0.768 AC: 2668 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital bile acid synthesis defect 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.032
DANN	Benign	0.63
PhyloP100		-2.7
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: rs1872930; hg19: chr7-137801444;