7-128410082-C-G

Variant names:

• chr7-128410082-C-G
• rs72624935
• NM_000883.4:c.-181G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000883.4(IMPDH1):​c.-181G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000578 in 443,202 control chromosomes in the GnomAD database, including 2 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 0.00027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (2 hom.)
• Consequence: IMPDH1 NM_000883.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 0 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):

• IMPDH1-related retinopathy

  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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Leber congenital amaurosis

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302195 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000269 (41/152368) while in subpopulation EAS AF = 0.00733 (38/5184). AF 95% confidence interval is 0.00549. There are 0 homozygotes in GnomAd4. There are 25 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 41 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	NM_000883.4	MANE Select	c.-181G>C		upstream_gene	N/A	NP_000874.2
	IMPDH1	NM_001102605.2		c.-181G>C		upstream_gene	N/A	NP_001096075.1	P20839-5
	IMPDH1	NM_001142576.2		c.-181G>C		upstream_gene	N/A	NP_001136048.1	P20839-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	ENST00000338791.11	TSL:2 MANE Select	c.-181G>C		upstream_gene	N/A	ENSP00000345096.6	P20839-6
	IMPDH1	ENST00000348127.11	TSL:1	c.-181G>C		upstream_gene	N/A	ENSP00000265385.8	P20839-3
	IMPDH1	ENST00000955327.1		c.-181G>C		upstream_gene	N/A	ENSP00000625386.1

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00731

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000739 AC: 215 AN: 290834 Hom.: 2 Cov.: 4 AF XY: 0.000721 AC XY: 107 AN XY: 148326

African (AFR) AF: 0.00 AC: 0 AN: 7086

American (AMR) AF: 0.00 AC: 0 AN: 7008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9416

East Asian (EAS) AF: 0.00973 AC: 212 AN: 21786

South Asian (SAS) AF: 0.00 AC: 0 AN: 9690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1394

European-Non Finnish (NFE) AF: 0.0000103 AC: 2 AN: 193780

Other (OTH) AF: 0.0000553 AC: 1 AN: 18096

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152368 Hom.: 0 Cov.: 33 AF XY: 0.000336 AC XY: 25 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00733 AC: 38 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000261

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.2
DANN	Benign	0.44
PhyloP100		-0.72
PromoterAI		0.0059	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs72624935; hg19: chr7-128050136;