rs11701944

chr21-42113033-A-G

Variant summary

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

The NM_001004416.3(UMODL1):c.2105-540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,698 control chromosomes in the GnomAD database, including 7,196 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 0.30 (7171 hom., cov: 32)
  • Exomes 𝑓: 0.24 (25 hom.)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.2105-540A>G		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.2105-540A>G		intron_variant		1	NM_001004416.3	P2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46122 AN: 151868 Hom.: 7155 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.237 AC: 169 AN: 712 Hom.: 25 Cov.: 0 AF XY: 0.254 AC XY: 103 AN XY: 406

Gnomad4 AMR exome AF: 0.143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.304 AC: 46188 AN: 151986 Hom.: 7171 Cov.: 32 AF XY: 0.309 AC XY: 22962 AN XY: 74320

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.288

Alfa AF: 0.274 Hom.: 1216

Bravo AF: 0.307

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.59
Dann	Benign	0.49

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: rs11701944; hg19: chr21-43533143; COSMIC: COSV61160451; COSMIC: COSV61160451;