rs1475911

Positions:

• chr21-42093370-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004416.3(UMODL1):​c.931+2932A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 153,100 control chromosomes in the GnomAD database, including 3,362 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 0.20 (3347 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15 hom.)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

Genes affected

UMODL1 (HGNC:12560): (uromodulin like 1) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in neutrophil migration. Predicted to act upstream of or within several processes, including adipose tissue development; cellular response to gonadotropin-releasing hormone; and regulation of ovarian follicle development. Predicted to be located in cytoplasm and external side of plasma membrane. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane; cell surface; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.931+2932A>C		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.931+2932A>C		intron_variant		1	NM_001004416.3	P2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30146 AN: 151878 Hom.: 3345 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.153 AC: 169 AN: 1104 Hom.: 15 Cov.: 0 AF XY: 0.155 AC XY: 92 AN XY: 594

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.0385

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.198 AC: 30160 AN: 151996 Hom.: 3347 Cov.: 32 AF XY: 0.206 AC XY: 15274 AN XY: 74292

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.183

Alfa AF: 0.195 Hom.: 371

Bravo AF: 0.194

Asia WGS AF: 0.342 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs1475911; hg19: chr21-43513480;