rs220145

Variant names:

• chr21-42118692-G-A
• rs220145
• NM_001004416.3:c.2476-419G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-42118692-G-A
• chr21-42118692-G-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.2476-419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,920 control chromosomes in the GnomAD database, including 3,354 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 0.21 (3354 hom., cov: 31)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 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.2476-419G>A		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.2860-419G>A		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.2644-419G>A		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.2476-419G>A		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.2860-419G>A		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.2644-419G>A		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31332 AN: 151802 Hom.: 3344 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.206 AC: 31361 AN: 151920 Hom.: 3354 Cov.: 31 AF XY: 0.208 AC XY: 15470 AN XY: 74250

African (AFR) AF: 0.158 AC: 6536 AN: 41450

American (AMR) AF: 0.282 AC: 4300 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1082 AN: 5152

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4806

European-Finnish (FIN) AF: 0.216 AC: 2281 AN: 10558

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.213 AC: 14438 AN: 67928

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.189 Hom.: 1198

Bravo AF: 0.211

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.51
PhyloP100		-0.23
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: rs220145; hg19: chr21-43538802; COSMIC: COSV68570485; COSMIC: COSV68570485;