7-138088545-T-G

Position:

• chr7-138088545-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005989.4(AKR1D1):​c.94-56T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,574,146 control chromosomes in the GnomAD database, including 436,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45829 hom., cov: 31)
  • Exomes 𝑓: 0.74 (390301 hom.)
• Consequence: AKR1D1 NM_005989.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 7-138088545-T-G is Benign according to our data. Variant chr7-138088545-T-G is described in ClinVar as [Benign]. Clinvar id is 1280935.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1D1	NM_005989.4	c.94-56T>G		intron_variant		ENST00000242375.8
AKR1D1	NM_001190906.2	c.94-56T>G		intron_variant
AKR1D1	NM_001190907.2	c.94-56T>G		intron_variant
AKR1D1	XM_047420763.1	c.94-3223T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1D1	ENST00000242375.8	c.94-56T>G		intron_variant		1	NM_005989.4	P1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117362 AN: 151984 Hom.: 45794 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.740 AC: 1051655 AN: 1422044 Hom.: 390301 AF XY: 0.740 AC XY: 525398 AN XY: 710016

Gnomad4 AFR exome AF: 0.885

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.752

Gnomad4 FIN exome AF: 0.759

Gnomad4 NFE exome AF: 0.742

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.772 AC: 117453 AN: 152102 Hom.: 45829 Cov.: 31 AF XY: 0.771 AC XY: 57293 AN XY: 74352

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.759

Alfa AF: 0.743 Hom.: 54467

Bravo AF: 0.768

Asia WGS AF: 0.721 AC: 2506 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.85

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: rs2120846; hg19: chr7-137773291; COSMIC: COSV54337922; COSMIC: COSV54337922;