7-128392776-G-A

Variant names:

• chr7-128392776-G-A
• rs1042267
• NM_000883.4:c.*231C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000883.4(IMPDH1):​c.*231C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 400,594 control chromosomes in the GnomAD database, including 1 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: not found (cov: 33)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: IMPDH1 NM_000883.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• 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):

• IMPDH1-related retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 11

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 10

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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=-0.68).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0002 (80/400594) while in subpopulation EAS AF = 0.00284 (79/27858). AF 95% confidence interval is 0.00233. There are 1 homozygotes in GnomAdExome4. There are 36 alleles in the male GnomAdExome4 subpopulation. Median coverage is 3. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 80 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.*231C>T		3_prime_UTR	Exon 17 of 17	NP_000874.2
	IMPDH1	NM_001102605.2		c.*231C>T		3_prime_UTR	Exon 16 of 16	NP_001096075.1	P20839-5
	IMPDH1	NM_001142576.2		c.*231C>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.*231C>T		3_prime_UTR	Exon 17 of 17	ENSP00000345096.6	P20839-6
	IMPDH1	ENST00000348127.11	TSL:1	c.*231C>T		3_prime_UTR	Exon 15 of 15	ENSP00000265385.8	P20839-3
	IMPDH1	ENST00000955327.1		c.*231C>T		3_prime_UTR	Exon 15 of 15	ENSP00000625386.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.000200 AC: 80 AN: 400594 Hom.: 1 Cov.: 3 AF XY: 0.000171 AC XY: 36 AN XY: 210762

African (AFR) AF: 0.00 AC: 0 AN: 11132

American (AMR) AF: 0.00 AC: 0 AN: 16910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12244

East Asian (EAS) AF: 0.00284 AC: 79 AN: 27858

South Asian (SAS) AF: 0.00 AC: 0 AN: 41512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 240086

Other (OTH) AF: 0.0000433 AC: 1 AN: 23106

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs1042267; hg19: chr7-128032830;