7-128394413-C-T

Variant names:

• chr7-128394413-C-T
• rs72624969
• NM_000883.4:c.1694+43G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000883.4(IMPDH1):​c.1694+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 1,613,460 control chromosomes in the GnomAD database, including 7,199 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 0.068 (740 hom., cov: 32)
  • Exomes 𝑓: 0.071 (6459 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 5 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 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.1694+43G>A		intron	N/A	NP_000874.2
	IMPDH1	NM_001102605.2		c.1664+43G>A		intron	N/A	NP_001096075.1	P20839-5
	IMPDH1	NM_001142576.2		c.1595+43G>A		intron	N/A	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.1694+43G>A		intron	N/A	ENSP00000345096.6	P20839-6
	IMPDH1	ENST00000348127.11	TSL:1	c.1586+43G>A		intron	N/A	ENSP00000265385.8	P20839-3
	IMPDH1	ENST00000955327.1		c.1682+43G>A		intron	N/A	ENSP00000625386.1

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 10307 AN: 151922 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0494

GnomAD2 exomes AF: 0.109 AC: 27331 AN: 251242 AF XY: 0.0997

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.0378

Gnomad EAS exome AF: 0.224

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.0589

Gnomad OTH exome AF: 0.0860

GnomAD4 exome AF: 0.0708 AC: 103443 AN: 1461420 Hom.: 6459 Cov.: 34 AF XY: 0.0699 AC XY: 50840 AN XY: 727040

African (AFR) AF: 0.0116 AC: 389 AN: 33478

American (AMR) AF: 0.296 AC: 13228 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0373 AC: 975 AN: 26134

East Asian (EAS) AF: 0.286 AC: 11337 AN: 39700

South Asian (SAS) AF: 0.0903 AC: 7783 AN: 86236

European-Finnish (FIN) AF: 0.0856 AC: 4567 AN: 53324

Middle Eastern (MID) AF: 0.0335 AC: 193 AN: 5766

European-Non Finnish (NFE) AF: 0.0548 AC: 60959 AN: 1111684

Other (OTH) AF: 0.0664 AC: 4012 AN: 60390

GnomAD4 genome AF: 0.0679 AC: 10320 AN: 152040 Hom.: 740 Cov.: 32 AF XY: 0.0730 AC XY: 5421 AN XY: 74288

African (AFR) AF: 0.0161 AC: 667 AN: 41512

American (AMR) AF: 0.204 AC: 3112 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1210 AN: 5128

South Asian (SAS) AF: 0.0873 AC: 420 AN: 4812

European-Finnish (FIN) AF: 0.0732 AC: 774 AN: 10576

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0570 AC: 3872 AN: 67966

Other (OTH) AF: 0.0479 AC: 101 AN: 2108

Alfa AF: 0.0344 Hom.: 41

Bravo AF: 0.0748

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.3
DANN	Benign	0.71
PhyloP100		-0.049
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: rs72624969; hg19: chr7-128034467; COSMIC: COSV58315397; COSMIC: COSV58315397;