NM_000883.4:c.579+119G>A

Variant names:

• chr7-128400698-C-T
• rs2278293
• NM_000883.4:c.579+119G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000883.4(IMPDH1):​c.579+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,180,866 control chromosomes in the GnomAD database, including 121,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (16500 hom., cov: 33)
  • Exomes 𝑓: 0.45 (105000 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 35 publications found

Genes affected

IMPDH1 (HGNC:6052): (inosine monophosphate dehydrogenase 1) The protein encoded by this gene acts as a homotetramer to regulate cell growth. The encoded protein is an enzyme that catalyzes the synthesis of xanthine monophosphate (XMP) from inosine-5'-monophosphate (IMP). This is the rate-limiting step in the de novo synthesis of guanine nucleotides. Defects in this gene are a cause of retinitis pigmentosa type 10 (RP10). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

IMPDH1 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 11

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa 10

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000883.4. 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
	IMPDH1	NM_000883.4	MANE Select	c.579+119G>A		intron	N/A	NP_000874.2
	IMPDH1	NM_001102605.2		c.549+119G>A		intron	N/A	NP_001096075.1
	IMPDH1	NM_001142576.2		c.480+119G>A		intron	N/A	NP_001136048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	ENST00000338791.11	TSL:2 MANE Select	c.579+119G>A		intron	N/A	ENSP00000345096.6
	IMPDH1	ENST00000348127.11	TSL:1	c.471+119G>A		intron	N/A	ENSP00000265385.8
	IMPDH1	ENST00000496487.5	TSL:4	n.518G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70638 AN: 151954 Hom.: 16498 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.473

GnomAD4 exome AF: 0.448 AC: 461360 AN: 1028794 Hom.: 105000 Cov.: 14 AF XY: 0.444 AC XY: 235718 AN XY: 530700

African (AFR) AF: 0.494 AC: 12361 AN: 25034

American (AMR) AF: 0.466 AC: 20414 AN: 43816

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 11957 AN: 23474

East Asian (EAS) AF: 0.393 AC: 14807 AN: 37630

South Asian (SAS) AF: 0.325 AC: 25161 AN: 77428

European-Finnish (FIN) AF: 0.506 AC: 26841 AN: 52998

Middle Eastern (MID) AF: 0.418 AC: 1507 AN: 3608

European-Non Finnish (NFE) AF: 0.456 AC: 327488 AN: 718758

Other (OTH) AF: 0.452 AC: 20824 AN: 46048

GnomAD4 genome AF: 0.465 AC: 70675 AN: 152072 Hom.: 16500 Cov.: 33 AF XY: 0.463 AC XY: 34410 AN XY: 74342

African (AFR) AF: 0.489 AC: 20300 AN: 41474

American (AMR) AF: 0.449 AC: 6867 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1755 AN: 3466

East Asian (EAS) AF: 0.409 AC: 2112 AN: 5166

South Asian (SAS) AF: 0.329 AC: 1588 AN: 4824

European-Finnish (FIN) AF: 0.509 AC: 5383 AN: 10584

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31164 AN: 67960

Other (OTH) AF: 0.474 AC: 1002 AN: 2114

Alfa AF: 0.461 Hom.: 37634

Bravo AF: 0.468

Asia WGS AF: 0.373 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.0060
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2278293; hg19: chr7-128040752; COSMIC: COSV58316192; COSMIC: COSV58316192;