NM_000883.4:c.-36T>C

Variant names:

• chr7-128409937-A-G
• rs72624937
• NM_000883.4:c.-36T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_000883.4(IMPDH1):​c.-36T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,329,552 control chromosomes in the GnomAD database, including 1 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 0.00076 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000069 (1 hom.)
• Consequence: IMPDH1 NM_000883.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988
• Publications: 1 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

ENSG00000302195 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000763 (116/152026) while in subpopulation AFR AF = 0.00263 (109/41468). AF 95% confidence interval is 0.00223. There are 0 homozygotes in GnomAd4. There are 59 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 116 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.-36T>C		5_prime_UTR_variant	Exon 1 of 17	ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.-36T>C		5_prime_UTR_variant	Exon 1 of 17	2	NM_000883.4	ENSP00000345096.6

Frequencies

GnomAD3 genomes AF: 0.000764 AC: 116 AN: 151920 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.000245 AC: 1 AN: 4088 AF XY: 0.000362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000688 AC: 81 AN: 1177526 Hom.: 1 Cov.: 30 AF XY: 0.0000616 AC XY: 35 AN XY: 567746

African (AFR) AF: 0.00249 AC: 58 AN: 23318

American (AMR) AF: 0.000319 AC: 3 AN: 9410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16098

East Asian (EAS) AF: 0.00 AC: 0 AN: 26802

South Asian (SAS) AF: 0.00 AC: 0 AN: 45038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3270

European-Non Finnish (NFE) AF: 0.00000205 AC: 2 AN: 977756

Other (OTH) AF: 0.000373 AC: 18 AN: 48286

GnomAD4 genome AF: 0.000763 AC: 116 AN: 152026 Hom.: 0 Cov.: 33 AF XY: 0.000794 AC XY: 59 AN XY: 74314

African (AFR) AF: 0.00263 AC: 109 AN: 41468

American (AMR) AF: 0.000261 AC: 4 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67906

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.93
PhyloP100		0.99
PromoterAI		-0.33	Neutral

Splicing

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

Other links and lift over

dbSNP: rs72624937; hg19: chr7-128049991;