chr1-45569881-C-G

Variant names:

• chr1-45569881-C-G
• rs139469824
• NM_153326.3:c.913-10C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_153326.3(AKR1A1):​c.913-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,613,584 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (13 hom.)
• Consequence: AKR1A1 NM_153326.3 intron
• Scores: Splicing: ADA: 0.0003279
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

AKR1A1 (HGNC:380): (aldo-keto reductase family 1 member A1) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member, also known as aldehyde reductase, is involved in the reduction of biogenic and xenobiotic aldehydes and is present in virtually every tissue. Multiple alternatively spliced transcript variants of this gene exist, all encoding the same protein. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 1-45569881-C-G is Benign according to our data. Variant chr1-45569881-C-G is described in ClinVar as Benign. ClinVar VariationId is 781662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153326.3. 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
	AKR1A1	NM_153326.3	MANE Select	c.913-10C>G		intron	N/A	NP_697021.1	P14550
	AKR1A1	NM_001202413.2		c.913-10C>G		intron	N/A	NP_001189342.1	P14550
	AKR1A1	NM_001202414.2		c.913-10C>G		intron	N/A	NP_001189343.1	P14550

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1A1	ENST00000351829.9	TSL:1 MANE Select	c.913-10C>G		intron	N/A	ENSP00000312606.4	P14550
	AKR1A1	ENST00000372070.7	TSL:1	c.913-10C>G		intron	N/A	ENSP00000361140.3	P14550
	AKR1A1	ENST00000863950.1		c.934-10C>G		intron	N/A	ENSP00000534009.1

Frequencies

GnomAD3 genomes AF: 0.00282 AC: 429 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00445

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00275 AC: 690 AN: 251034 AF XY: 0.00282

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00306

Gnomad NFE exome AF: 0.00457

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00340 AC: 4961 AN: 1461248 Hom.: 13 Cov.: 30 AF XY: 0.00330 AC XY: 2401 AN XY: 727002

African (AFR) AF: 0.000717 AC: 24 AN: 33468

American (AMR) AF: 0.00125 AC: 56 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00283 AC: 74 AN: 26120

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86240

European-Finnish (FIN) AF: 0.00362 AC: 193 AN: 53366

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00400 AC: 4442 AN: 1111496

Other (OTH) AF: 0.00272 AC: 164 AN: 60372

GnomAD4 genome AF: 0.00282 AC: 429 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.00258 AC XY: 192 AN XY: 74488

African (AFR) AF: 0.000866 AC: 36 AN: 41574

American (AMR) AF: 0.00307 AC: 47 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00445 AC: 303 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00216 Hom.: 0

Bravo AF: 0.00249

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.5
DANN	Benign	0.71
PhyloP100		-1.2
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00033
dbscSNV1_RF	Benign	0.036
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: rs139469824; hg19: chr1-46035553;