rs72624968

chr7-128394423-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000883.4(IMPDH1):c.1694+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,613,944 control chromosomes in the GnomAD database, including 170 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 0.0099 (15 hom., cov: 32)
  • Exomes 𝑓: 0.014 (155 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00987 (1502/152236) while in subpopulation NFE AF= 0.0149 (1016/68012). AF 95% confidence interval is 0.0142. There are 15 homozygotes in gnomad4. There are 692 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1502 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPDH1	NM_000883.4	c.1694+33C>T		intron_variant		ENST00000338791.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPDH1	ENST00000338791.11	c.1694+33C>T		intron_variant		2	NM_000883.4

Frequencies

GnomAD3 genomes AF: 0.00987 AC: 1502 AN: 152118 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0103 AC: 2590 AN: 251294 Hom.: 20 AF XY: 0.0102 AC XY: 1392 AN XY: 135838

Gnomad AFR exome AF: 0.00369

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.0149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00307

Gnomad FIN exome AF: 0.00576

Gnomad NFE exome AF: 0.0147

Gnomad OTH exome AF: 0.0174

GnomAD4 exome AF: 0.0137 AC: 19962 AN: 1461708 Hom.: 155 Cov.: 34 AF XY: 0.0133 AC XY: 9660 AN XY: 727158

Gnomad4 AFR exome AF: 0.00248

Gnomad4 AMR exome AF: 0.0117

Gnomad4 ASJ exome AF: 0.0166

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00291

Gnomad4 FIN exome AF: 0.00534

Gnomad4 NFE exome AF: 0.0159

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.00987 AC: 1502 AN: 152236 Hom.: 15 Cov.: 32 AF XY: 0.00930 AC XY: 692 AN XY: 74418

Gnomad4 AFR AF: 0.00349

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00509

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0138 Hom.: 6

Bravo AF: 0.0103

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	8.2
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs72624968; hg19: chr7-128034477;