rs72624936

Variant names:

• chr7-128409970-A-C
• rs72624936
• NM_000883.4:c.-69T>G

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.-69T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,270,174 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (49 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (37 hom.)
• Consequence: IMPDH1 NM_000883.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0660
• 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: 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

ENSG00000302195 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-128409970-A-C is Benign according to our data. Variant chr7-128409970-A-C is described in ClinVar as Benign. ClinVar VariationId is 358882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 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.-69T>G		5_prime_UTR	Exon 1 of 17	NP_000874.2
	IMPDH1	NM_001102605.2		c.-69T>G		5_prime_UTR	Exon 1 of 16	NP_001096075.1	P20839-5
	IMPDH1	NM_001142576.2		c.-69T>G		5_prime_UTR	Exon 1 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.-69T>G		5_prime_UTR	Exon 1 of 17	ENSP00000345096.6	P20839-6
	IMPDH1	ENST00000348127.11	TSL:1	c.-69T>G		5_prime_UTR	Exon 1 of 15	ENSP00000265385.8	P20839-3
	IMPDH1	ENST00000354269.9	TSL:2	c.-69T>G		5_prime_UTR	Exon 1 of 16	ENSP00000346219.5	P20839-5

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2128 AN: 152064 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00718

GnomAD4 exome AF: 0.00125 AC: 1401 AN: 1118002 Hom.: 37 Cov.: 20 AF XY: 0.00113 AC XY: 606 AN XY: 536236

African (AFR) AF: 0.0528 AC: 1180 AN: 22352

American (AMR) AF: 0.00216 AC: 18 AN: 8344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15174

East Asian (EAS) AF: 0.00 AC: 0 AN: 26112

South Asian (SAS) AF: 0.00 AC: 0 AN: 37394

European-Finnish (FIN) AF: 0.0000389 AC: 1 AN: 25726

Middle Eastern (MID) AF: 0.00226 AC: 7 AN: 3104

European-Non Finnish (NFE) AF: 0.0000685 AC: 64 AN: 934048

Other (OTH) AF: 0.00286 AC: 131 AN: 45748

GnomAD4 genome AF: 0.0140 AC: 2133 AN: 152172 Hom.: 49 Cov.: 33 AF XY: 0.0133 AC XY: 993 AN XY: 74406

African (AFR) AF: 0.0495 AC: 2057 AN: 41538

American (AMR) AF: 0.00353 AC: 54 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67960

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00971 Hom.: 2

Bravo AF: 0.0160

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis 11 (1)
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.63
PhyloP100		0.066
PromoterAI		0.085	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs72624936; hg19: chr7-128050024;