rs220281

Variant names:

• chr21-42073477-G-A
• rs220281
• NM_001004416.3:c.76+2085G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-42073477-G-A
• chr21-42073477-G-C

Variant summary

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

The NM_001004416.3(UMODL1):​c.76+2085G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,010 control chromosomes in the GnomAD database, including 32,360 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 0.65 (32360 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.76+2085G>A		intron_variant	Intron 1 of 22	ENST00000408910.7	NP_001004416.3
UMODL1	NM_173568.4	c.76+2085G>A		intron_variant	Intron 1 of 21		NP_775839.4
UMODL1	NM_001199527.3	c.-140-2528G>A		intron_variant	Intron 1 of 21		NP_001186456.2
UMODL1	NM_001199528.4	c.-140-2528G>A		intron_variant	Intron 1 of 22		NP_001186457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.76+2085G>A		intron_variant	Intron 1 of 22	1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.76+2085G>A		intron_variant	Intron 1 of 21	1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.-140-2528G>A		intron_variant	Intron 1 of 21	1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.-140-2528G>A		intron_variant	Intron 1 of 22	1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98377 AN: 151892 Hom.: 32328 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.648 AC: 98457 AN: 152010 Hom.: 32360 Cov.: 32 AF XY: 0.647 AC XY: 48039 AN XY: 74294

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.636

Alfa AF: 0.679 Hom.: 45774

Bravo AF: 0.650

Asia WGS AF: 0.420 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.58

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: rs220281; hg19: chr21-43493586;