chr7-128392373-G-A

Variant names:

• chr7-128392373-G-A
• rs1803822
• NM_000883.4:c.*634C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_000883.4(IMPDH1):​c.*634C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0177 in 154,144 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (39 hom., cov: 33)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: IMPDH1 NM_000883.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.03
• Publications: 4 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

ENSG00000294385 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 7-128392373-G-A is Benign according to our data. Variant chr7-128392373-G-A is described in ClinVar as Benign. ClinVar VariationId is 358858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0178 (2707/152362) while in subpopulation SAS AF = 0.055 (266/4834). AF 95% confidence interval is 0.0496. There are 39 homozygotes in GnomAd4. There are 1329 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2707 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.*634C>T		3_prime_UTR	Exon 17 of 17	NP_000874.2
	IMPDH1	NM_001102605.2		c.*634C>T		3_prime_UTR	Exon 16 of 16	NP_001096075.1	P20839-5
	IMPDH1	NM_001142576.2		c.*634C>T		3_prime_UTR	Exon 16 of 16	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.*634C>T		3_prime_UTR	Exon 17 of 17	ENSP00000345096.6	P20839-6
	IMPDH1	ENST00000348127.11	TSL:1	c.*634C>T		3_prime_UTR	Exon 15 of 15	ENSP00000265385.8	P20839-3
	IMPDH1	ENST00000955327.1		c.*634C>T		3_prime_UTR	Exon 15 of 15	ENSP00000625386.1

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2709 AN: 152244 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.00615

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.0135 AC: 24 AN: 1782 Hom.: 0 Cov.: 0 AF XY: 0.0144 AC XY: 14 AN XY: 970

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00538 AC: 1 AN: 186

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 1 AN: 12

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.0581 AC: 5 AN: 86

European-Finnish (FIN) AF: 0.00214 AC: 1 AN: 468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0169 AC: 16 AN: 948

Other (OTH) AF: 0.00 AC: 0 AN: 74

GnomAD4 genome AF: 0.0178 AC: 2707 AN: 152362 Hom.: 39 Cov.: 33 AF XY: 0.0178 AC XY: 1329 AN XY: 74510

African (AFR) AF: 0.00613 AC: 255 AN: 41592

American (AMR) AF: 0.0195 AC: 298 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0550 AC: 266 AN: 4834

European-Finnish (FIN) AF: 0.00668 AC: 71 AN: 10628

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0248 AC: 1688 AN: 68028

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0198 Hom.: 5

Bravo AF: 0.0170

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis 11 (1)
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.93
PhyloP100		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1803822; hg19: chr7-128032427;