rs2839468

Variant names:

• chr21-42117983-A-C
• rs2839468
• NM_001004416.3:c.2476-1128A>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.2476-1128A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,934 control chromosomes in the GnomAD database, including 14,774 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 (14774 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.2476-1128A>C		intron_variant	Intron 14 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.2476-1128A>C		intron_variant	Intron 14 of 22	1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.2860-1128A>C		intron_variant	Intron 13 of 21	1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.2644-1128A>C		intron_variant	Intron 13 of 21	1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.2260-1128A>C		intron_variant	Intron 14 of 22	1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66762 AN: 151816 Hom.: 14766 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.440 AC: 66809 AN: 151934 Hom.: 14774 Cov.: 32 AF XY: 0.436 AC XY: 32355 AN XY: 74270

African (AFR) AF: 0.478 AC: 19782 AN: 41398

American (AMR) AF: 0.433 AC: 6610 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3468

East Asian (EAS) AF: 0.479 AC: 2478 AN: 5168

South Asian (SAS) AF: 0.468 AC: 2249 AN: 4806

European-Finnish (FIN) AF: 0.344 AC: 3623 AN: 10544

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29158 AN: 67968

Other (OTH) AF: 0.457 AC: 963 AN: 2106

Alfa AF: 0.438 Hom.: 26608

Bravo AF: 0.448

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.66
PhyloP100		-0.91
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: rs2839468; hg19: chr21-43538093; COSMIC: COSV68570531; COSMIC: COSV68570531;