7-128400925-G-T

Variant names:

• chr7-128400925-G-T
• rs72624952
• NM_000883.4:c.505-34C>A

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.505-34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,604,996 control chromosomes in the GnomAD database, including 312 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 0.012 (21 hom., cov: 33)
  • Exomes 𝑓: 0.018 (291 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0124 (1882/152220) while in subpopulation NFE AF = 0.0211 (1436/68022). AF 95% confidence interval is 0.0202. There are 21 homozygotes in GnomAd4. There are 868 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1882 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.505-34C>A		intron_variant	Intron 6 of 16	ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.505-34C>A		intron_variant	Intron 6 of 16	2	NM_000883.4	ENSP00000345096.6

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1883 AN: 152102 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00341

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.0128 AC: 3227 AN: 251296 AF XY: 0.0129

Gnomad AFR exome AF: 0.00425

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00367

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0211

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.0180 AC: 26149 AN: 1452776 Hom.: 291 Cov.: 30 AF XY: 0.0175 AC XY: 12690 AN XY: 723250

African (AFR) AF: 0.00285 AC: 95 AN: 33294

American (AMR) AF: 0.00526 AC: 235 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00468 AC: 122 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00130 AC: 112 AN: 86056

European-Finnish (FIN) AF: 0.0211 AC: 1128 AN: 53408

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5752

European-Non Finnish (NFE) AF: 0.0215 AC: 23726 AN: 1103726

Other (OTH) AF: 0.0120 AC: 719 AN: 60106

GnomAD4 genome AF: 0.0124 AC: 1882 AN: 152220 Hom.: 21 Cov.: 33 AF XY: 0.0117 AC XY: 868 AN XY: 74412

African (AFR) AF: 0.00340 AC: 141 AN: 41524

American (AMR) AF: 0.00490 AC: 75 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.0190 AC: 201 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0211 AC: 1436 AN: 68022

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.0139 Hom.: 3

Bravo AF: 0.0107

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.80
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs72624952; hg19: chr7-128040979; COSMIC: COSV58317411; COSMIC: COSV58317411;