7-128403981-A-G

Variant names:

• chr7-128403981-A-G
• rs2288549
• NM_000883.4:c.354-227T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000883.4(IMPDH1):​c.354-227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,230 control chromosomes in the GnomAD database, including 47,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.78 (47068 hom., cov: 33)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.422
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-128403981-A-G is Benign according to our data. Variant chr7-128403981-A-G is described in ClinVar as Benign. ClinVar VariationId is 1252510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	NM_000883.4	MANE Select	c.354-227T>C		intron	N/A	NP_000874.2
	IMPDH1	NM_001102605.2		c.324-227T>C		intron	N/A	NP_001096075.1
	IMPDH1	NM_001142576.2		c.255-227T>C		intron	N/A	NP_001136048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	ENST00000338791.11	TSL:2 MANE Select	c.354-227T>C		intron	N/A	ENSP00000345096.6
	IMPDH1	ENST00000348127.11	TSL:1	c.246-227T>C		intron	N/A	ENSP00000265385.8
	IMPDH1	ENST00000354269.9	TSL:2	c.324-227T>C		intron	N/A	ENSP00000346219.5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119320 AN: 152112 Hom.: 47026 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.777

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.784 AC: 119423 AN: 152230 Hom.: 47068 Cov.: 33 AF XY: 0.789 AC XY: 58700 AN XY: 74422

African (AFR) AF: 0.823 AC: 34196 AN: 41542

American (AMR) AF: 0.794 AC: 12139 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2608 AN: 3472

East Asian (EAS) AF: 0.939 AC: 4870 AN: 5184

South Asian (SAS) AF: 0.827 AC: 3989 AN: 4822

European-Finnish (FIN) AF: 0.793 AC: 8400 AN: 10590

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50866 AN: 68008

Other (OTH) AF: 0.780 AC: 1651 AN: 2116

Alfa AF: 0.765 Hom.: 35332

Bravo AF: 0.784

Asia WGS AF: 0.904 AC: 3145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.55
PhyloP100		0.42
PromoterAI		0.0036	Neutral
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: rs2288549; hg19: chr7-128044035;