chr7-128395076-AC-A

Variant names:

• chr7-128395076-AC-A
• rs72624966
• NM_000883.4:c.1406-44delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000883.4(IMPDH1):​c.1406-44delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 1,612,738 control chromosomes in the GnomAD database, including 2,258 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (219 hom., cov: 32)
  • Exomes 𝑓: 0.037 (2039 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.188
• 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 -10 ACMG points.

• BP6: Variant 7-128395076-AC-A is Benign according to our data. Variant chr7-128395076-AC-A is described in ClinVar as Benign. ClinVar VariationId is 1259283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	NM_000883.4	MANE Select	c.1406-44delG		intron	N/A	NP_000874.2
	IMPDH1	NM_001102605.2		c.1376-44delG		intron	N/A	NP_001096075.1
	IMPDH1	NM_001142576.2		c.1307-44delG		intron	N/A	NP_001136048.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	ENST00000338791.11	TSL:2 MANE Select	c.1406-44delG		intron	N/A	ENSP00000345096.6
	IMPDH1	ENST00000348127.11	TSL:1	c.1298-44delG		intron	N/A	ENSP00000265385.8
	IMPDH1	ENST00000955327.1		c.1394-44delG		intron	N/A	ENSP00000625386.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5240 AN: 151312 Hom.: 219 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0673

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.00771

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0434

GnomAD2 exomes AF: 0.0534 AC: 13365 AN: 250410 AF XY: 0.0566

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0272

Gnomad ASJ exome AF: 0.0628

Gnomad EAS exome AF: 0.216

Gnomad FIN exome AF: 0.00678

Gnomad NFE exome AF: 0.0266

Gnomad OTH exome AF: 0.0469

GnomAD4 exome AF: 0.0371 AC: 54171 AN: 1461312 Hom.: 2039 Cov.: 32 AF XY: 0.0398 AC XY: 28909 AN XY: 726978

African (AFR) AF: 0.0188 AC: 630 AN: 33478

American (AMR) AF: 0.0285 AC: 1274 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 1697 AN: 26134

East Asian (EAS) AF: 0.176 AC: 6998 AN: 39700

South Asian (SAS) AF: 0.127 AC: 10929 AN: 86254

European-Finnish (FIN) AF: 0.00789 AC: 418 AN: 52962

Middle Eastern (MID) AF: 0.0629 AC: 363 AN: 5768

European-Non Finnish (NFE) AF: 0.0260 AC: 28919 AN: 1111912

Other (OTH) AF: 0.0487 AC: 2943 AN: 60386

GnomAD4 genome AF: 0.0346 AC: 5233 AN: 151426 Hom.: 219 Cov.: 32 AF XY: 0.0365 AC XY: 2698 AN XY: 73952

African (AFR) AF: 0.0189 AC: 782 AN: 41268

American (AMR) AF: 0.0312 AC: 474 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0673 AC: 233 AN: 3460

East Asian (EAS) AF: 0.210 AC: 1075 AN: 5118

South Asian (SAS) AF: 0.136 AC: 647 AN: 4760

European-Finnish (FIN) AF: 0.00771 AC: 81 AN: 10512

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1826 AN: 67820

Other (OTH) AF: 0.0435 AC: 91 AN: 2094

Alfa AF: 0.0177 Hom.: 14

Bravo AF: 0.0354

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs72624966; hg19: chr7-128035130; COSMIC: COSV58318127; COSMIC: COSV58318127;