chr21-42119937-C-A

Variant names:

• chr21-42119937-C-A
• rs220148
• NM_001004416.3:c.2689+613C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004416.3(UMODL1):​c.2689+613C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,094 control chromosomes in the GnomAD database, including 36,283 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 0.69 (36283 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004416.3. 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
	UMODL1	NM_001004416.3	MANE Select	c.2689+613C>A		intron	N/A	NP_001004416.3	Q5DID0-1
	UMODL1	NM_173568.4		c.3073+613C>A		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.2857+613C>A		intron	N/A	NP_001186456.2	Q5DID0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.2689+613C>A		intron	N/A	ENSP00000386147.2	Q5DID0-1
	UMODL1	ENST00000408989.6	TSL:1	c.3073+613C>A		intron	N/A	ENSP00000386126.2	Q5DID0-2
	UMODL1	ENST00000400427.5	TSL:1	c.2857+613C>A		intron	N/A	ENSP00000383279.1	Q5DID0-4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104532 AN: 151976 Hom.: 36229 Cov.: 33

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.688 AC: 104651 AN: 152094 Hom.: 36283 Cov.: 33 AF XY: 0.686 AC XY: 50969 AN XY: 74350

African (AFR) AF: 0.761 AC: 31599 AN: 41504

American (AMR) AF: 0.733 AC: 11209 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2419 AN: 3472

East Asian (EAS) AF: 0.701 AC: 3628 AN: 5174

South Asian (SAS) AF: 0.713 AC: 3444 AN: 4828

European-Finnish (FIN) AF: 0.563 AC: 5937 AN: 10536

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44071 AN: 67976

Other (OTH) AF: 0.690 AC: 1461 AN: 2116

Alfa AF: 0.666 Hom.: 108664

Bravo AF: 0.705

Asia WGS AF: 0.705 AC: 2449 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.64
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs220148; hg19: chr21-43540047;