NM_001004416.3:c.3776-1887T>C

Variant names:

• chr21-42135552-T-C
• rs220171
• NM_001004416.3:c.3776-1887T>C

Variant summary

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

The NM_001004416.3(UMODL1):​c.3776-1887T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,982 control chromosomes in the GnomAD database, including 15,302 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 0.44 (15302 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	NM_001004416.3	MANE Select	c.3776-1887T>C		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.4160-1887T>C		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3944-1887T>C		intron	N/A	NP_001186456.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.3776-1887T>C		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.4160-1887T>C		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.3944-1887T>C		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67149 AN: 151862 Hom.: 15264 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.442 AC: 67244 AN: 151982 Hom.: 15302 Cov.: 32 AF XY: 0.445 AC XY: 33063 AN XY: 74284

African (AFR) AF: 0.451 AC: 18672 AN: 41436

American (AMR) AF: 0.516 AC: 7886 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1531 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3584 AN: 5172

South Asian (SAS) AF: 0.456 AC: 2193 AN: 4814

European-Finnish (FIN) AF: 0.423 AC: 4471 AN: 10562

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27421 AN: 67934

Other (OTH) AF: 0.443 AC: 932 AN: 2106

Alfa AF: 0.413 Hom.: 20110

Bravo AF: 0.452

Asia WGS AF: 0.571 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.26
PhyloP100		-1.1
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: rs220171; hg19: chr21-43555662;