chr7-128395098-G-A

Variant names:

• chr7-128395098-G-A
• rs28580600
• NM_000883.4:c.1405+33C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000883.4(IMPDH1):​c.1405+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,794 control chromosomes in the GnomAD database, including 13,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1236 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11815 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.73
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-128395098-G-A is Benign according to our data. Variant chr7-128395098-G-A is described in ClinVar as [Benign]. Clinvar id is 1291045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.1405+33C>T		intron_variant	Intron 13 of 16	ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.1405+33C>T		intron_variant	Intron 13 of 16	2	NM_000883.4	ENSP00000345096.6

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19018 AN: 152098 Hom.: 1235 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.104 AC: 26137 AN: 251140 AF XY: 0.103

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0739

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.122 AC: 178238 AN: 1461578 Hom.: 11815 Cov.: 35 AF XY: 0.120 AC XY: 86983 AN XY: 727102

African (AFR) AF: 0.148 AC: 4949 AN: 33480

American (AMR) AF: 0.0801 AC: 3581 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3593 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0310 AC: 2671 AN: 86256

European-Finnish (FIN) AF: 0.118 AC: 6286 AN: 53124

Middle Eastern (MID) AF: 0.131 AC: 757 AN: 5768

European-Non Finnish (NFE) AF: 0.134 AC: 149019 AN: 1111994

Other (OTH) AF: 0.122 AC: 7372 AN: 60396

GnomAD4 genome AF: 0.125 AC: 19030 AN: 152216 Hom.: 1236 Cov.: 33 AF XY: 0.121 AC XY: 8991 AN XY: 74428

African (AFR) AF: 0.144 AC: 5978 AN: 41530

American (AMR) AF: 0.0977 AC: 1494 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4830

European-Finnish (FIN) AF: 0.120 AC: 1270 AN: 10604

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9163 AN: 68004

Other (OTH) AF: 0.148 AC: 313 AN: 2110

Alfa AF: 0.0870 Hom.: 148

Bravo AF: 0.128

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.013
DANN	Benign	0.35
PhyloP100		-1.7
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: rs28580600; hg19: chr7-128035152;