rs220155

Variant names:

• chr21-42124920-C-T
• rs220155
• NM_001004416.3:c.3148-1425C>T

Variant summary

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

The NM_001004416.3(UMODL1):​c.3148-1425C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,028 control chromosomes in the GnomAD database, including 14,720 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 (14720 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.515 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.3148-1425C>T		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.3532-1425C>T		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3316-1425C>T		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.3148-1425C>T		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.3532-1425C>T		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.3316-1425C>T		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66524 AN: 151910 Hom.: 14686 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.438 AC: 66605 AN: 152028 Hom.: 14720 Cov.: 32 AF XY: 0.437 AC XY: 32479 AN XY: 74296

African (AFR) AF: 0.419 AC: 17371 AN: 41466

American (AMR) AF: 0.524 AC: 8012 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1726 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2097 AN: 5158

South Asian (SAS) AF: 0.486 AC: 2335 AN: 4808

European-Finnish (FIN) AF: 0.391 AC: 4129 AN: 10564

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29368 AN: 67958

Other (OTH) AF: 0.446 AC: 943 AN: 2112

Alfa AF: 0.443 Hom.: 26314

Bravo AF: 0.448

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		-0.062
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: rs220155; hg19: chr21-43545030;