rs4731447

Variant names:

• chr7-128394713-A-C
• rs4731447
• NM_000883.4:c.1551-114T>G

Variant summary

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

The NM_000883.4(IMPDH1):​c.1551-114T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 1,444,702 control chromosomes in the GnomAD database, including 6,695 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 0.074 (774 hom., cov: 32)
  • Exomes 𝑓: 0.072 (5921 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.1551-114T>G		intron_variant	Intron 14 of 16	ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.1551-114T>G		intron_variant	Intron 14 of 16	2	NM_000883.4	ENSP00000345096.6

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11197 AN: 152052 Hom.: 769 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0533

GnomAD4 exome AF: 0.0717 AC: 92686 AN: 1292532 Hom.: 5921 Cov.: 19 AF XY: 0.0708 AC XY: 45974 AN XY: 649280

African (AFR) AF: 0.0328 AC: 992 AN: 30288

American (AMR) AF: 0.296 AC: 12031 AN: 40708

Ashkenazi Jewish (ASJ) AF: 0.0373 AC: 930 AN: 24934

East Asian (EAS) AF: 0.288 AC: 10906 AN: 37928

South Asian (SAS) AF: 0.0898 AC: 7324 AN: 81570

European-Finnish (FIN) AF: 0.0869 AC: 3583 AN: 41216

Middle Eastern (MID) AF: 0.0365 AC: 154 AN: 4224

European-Non Finnish (NFE) AF: 0.0543 AC: 53057 AN: 976674

Other (OTH) AF: 0.0674 AC: 3709 AN: 54990

GnomAD4 genome AF: 0.0737 AC: 11217 AN: 152170 Hom.: 774 Cov.: 32 AF XY: 0.0787 AC XY: 5855 AN XY: 74380

African (AFR) AF: 0.0353 AC: 1466 AN: 41540

American (AMR) AF: 0.207 AC: 3170 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3472

East Asian (EAS) AF: 0.236 AC: 1213 AN: 5146

South Asian (SAS) AF: 0.0883 AC: 426 AN: 4826

European-Finnish (FIN) AF: 0.0734 AC: 778 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0572 AC: 3888 AN: 67994

Other (OTH) AF: 0.0518 AC: 109 AN: 2104

Alfa AF: 0.0604 Hom.: 61

Bravo AF: 0.0813

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.054
DANN	Benign	0.38
PhyloP100		-3.0
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: rs4731447; hg19: chr7-128034767;