rs17169518

Variant names:

• chr7-138113680-G-A
• rs17169518
• NM_005989.4:c.856-10G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-138113680-G-A
• chr7-138113680-G-C

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.856-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 1,611,990 control chromosomes in the GnomAD database, including 1,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (192 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1428 hom.)
• Consequence: AKR1D1 NM_005989.4 intron
• Scores: Splicing: ADA: 0.00001887
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.34
• Publications: 5 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=-0.98).
• BP6: Variant 7-138113680-G-A is Benign according to our data. Variant chr7-138113680-G-A is described in ClinVar as Benign. ClinVar VariationId is 259894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0642 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1D1	NM_005989.4	MANE Select	c.856-10G>A		intron	N/A	NP_005980.1
	AKR1D1	NM_001190907.2		c.856-2940G>A		intron	N/A	NP_001177836.1
	AKR1D1	NM_001190906.2		c.733-10G>A		intron	N/A	NP_001177835.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1D1	ENST00000242375.8	TSL:1 MANE Select	c.856-10G>A		intron	N/A	ENSP00000242375.3
	AKR1D1	ENST00000432161.5	TSL:2	c.856-2940G>A		intron	N/A	ENSP00000389197.1
	AKR1D1	ENST00000411726.6	TSL:2	c.733-10G>A		intron	N/A	ENSP00000402374.2

Frequencies

GnomAD3 genomes AF: 0.0454 AC: 6909 AN: 152082 Hom.: 192 Cov.: 32

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0512

GnomAD2 exomes AF: 0.0339 AC: 8503 AN: 250802 AF XY: 0.0333

Gnomad AFR exome AF: 0.0675

Gnomad AMR exome AF: 0.0203

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.00120

Gnomad FIN exome AF: 0.0446

Gnomad NFE exome AF: 0.0404

Gnomad OTH exome AF: 0.0418

GnomAD4 exome AF: 0.0408 AC: 59600 AN: 1459790 Hom.: 1428 Cov.: 30 AF XY: 0.0401 AC XY: 29152 AN XY: 726338

African (AFR) AF: 0.0699 AC: 2336 AN: 33442

American (AMR) AF: 0.0220 AC: 982 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0247 AC: 645 AN: 26130

East Asian (EAS) AF: 0.00101 AC: 40 AN: 39682

South Asian (SAS) AF: 0.0206 AC: 1778 AN: 86200

European-Finnish (FIN) AF: 0.0445 AC: 2376 AN: 53364

Middle Eastern (MID) AF: 0.0336 AC: 194 AN: 5768

European-Non Finnish (NFE) AF: 0.0440 AC: 48896 AN: 1110196

Other (OTH) AF: 0.0390 AC: 2353 AN: 60308

GnomAD4 genome AF: 0.0454 AC: 6912 AN: 152200 Hom.: 192 Cov.: 32 AF XY: 0.0443 AC XY: 3299 AN XY: 74418

African (AFR) AF: 0.0663 AC: 2751 AN: 41516

American (AMR) AF: 0.0268 AC: 409 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5188

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4822

European-Finnish (FIN) AF: 0.0415 AC: 440 AN: 10596

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0437 AC: 2969 AN: 68002

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0434 Hom.: 152

Bravo AF: 0.0455

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Congenital bile acid synthesis defect 2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0070
DANN	Benign	0.67
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.020		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: rs17169518; hg19: chr7-137798426;