21-42117384-A-G

Variant names:

• chr21-42117384-A-G
• rs220143
• NM_001004416.3:c.2475+1399A>G

Variant summary

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

The NM_001004416.3(UMODL1):​c.2475+1399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,118 control chromosomes in the GnomAD database, including 31,767 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 0.64 (31767 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.706 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.2475+1399A>G		intron	N/A	NP_001004416.3	Q5DID0-1
	UMODL1	NM_173568.4		c.2859+1399A>G		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.2643+1399A>G		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.2475+1399A>G		intron	N/A	ENSP00000386147.2	Q5DID0-1
	UMODL1	ENST00000408989.6	TSL:1	c.2859+1399A>G		intron	N/A	ENSP00000386126.2	Q5DID0-2
	UMODL1	ENST00000400427.5	TSL:1	c.2643+1399A>G		intron	N/A	ENSP00000383279.1	Q5DID0-4

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97966 AN: 152002 Hom.: 31734 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.645 AC: 98050 AN: 152118 Hom.: 31767 Cov.: 32 AF XY: 0.643 AC XY: 47827 AN XY: 74372

African (AFR) AF: 0.593 AC: 24593 AN: 41476

American (AMR) AF: 0.717 AC: 10961 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2418 AN: 3472

East Asian (EAS) AF: 0.717 AC: 3710 AN: 5174

South Asian (SAS) AF: 0.720 AC: 3463 AN: 4812

European-Finnish (FIN) AF: 0.562 AC: 5960 AN: 10596

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44664 AN: 67986

Other (OTH) AF: 0.657 AC: 1387 AN: 2112

Alfa AF: 0.641 Hom.: 18585

Bravo AF: 0.654

Asia WGS AF: 0.705 AC: 2450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.094
DANN	Benign	0.55
PhyloP100		-1.3
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: rs220143; hg19: chr21-43537494;