rs220153

Variant names:

• chr21-42124513-G-A
• rs220153
• NM_001004416.3:c.3147+1363G>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.3147+1363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,102 control chromosomes in the GnomAD database, including 5,525 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 0.26 (5525 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 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.3147+1363G>A		intron	N/A	NP_001004416.3	Q5DID0-1
	UMODL1	NM_173568.4		c.3531+1363G>A		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3315+1363G>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.3147+1363G>A		intron	N/A	ENSP00000386147.2	Q5DID0-1
	UMODL1	ENST00000408989.6	TSL:1	c.3531+1363G>A		intron	N/A	ENSP00000386126.2	Q5DID0-2
	UMODL1	ENST00000400427.5	TSL:1	c.3315+1363G>A		intron	N/A	ENSP00000383279.1	Q5DID0-4

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39887 AN: 151984 Hom.: 5513 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.263 AC: 39934 AN: 152102 Hom.: 5525 Cov.: 32 AF XY: 0.264 AC XY: 19648 AN XY: 74352

African (AFR) AF: 0.176 AC: 7321 AN: 41504

American (AMR) AF: 0.340 AC: 5194 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5164

South Asian (SAS) AF: 0.263 AC: 1263 AN: 4810

European-Finnish (FIN) AF: 0.278 AC: 2947 AN: 10602

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19825 AN: 67956

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.289 Hom.: 11380

Bravo AF: 0.266

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.79
PhyloP100		0.68
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: rs220153; hg19: chr21-43544623; COSMIC: COSV68569334; COSMIC: COSV68569334;