NM_001004416.3:c.2104+28C>T

Variant names:

• chr21-42111738-C-T
• rs220131
• NM_001004416.3:c.2104+28C>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.2104+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,579,198 control chromosomes in the GnomAD database, including 201,737 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 0.43 (15308 hom., cov: 33)
  • Exomes 𝑓: 0.51 (186429 hom.)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 9 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 (NFE) allele frequency at 95% confidence interval = 0.516 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.2104+28C>T		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.2488+28C>T		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.2272+28C>T		intron	N/A	NP_001186456.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.2104+28C>T		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.2488+28C>T		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.2272+28C>T		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65321 AN: 151958 Hom.: 15316 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.455

GnomAD2 exomes AF: 0.479 AC: 105189 AN: 219374 AF XY: 0.479

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.519

Gnomad OTH exome AF: 0.502

GnomAD4 exome AF: 0.507 AC: 723923 AN: 1427120 Hom.: 186429 Cov.: 32 AF XY: 0.504 AC XY: 356158 AN XY: 706612

African (AFR) AF: 0.213 AC: 7003 AN: 32888

American (AMR) AF: 0.482 AC: 20618 AN: 42812

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 11500 AN: 24128

East Asian (EAS) AF: 0.489 AC: 19164 AN: 39194

South Asian (SAS) AF: 0.393 AC: 32078 AN: 81672

European-Finnish (FIN) AF: 0.552 AC: 26727 AN: 48424

Middle Eastern (MID) AF: 0.430 AC: 2430 AN: 5652

European-Non Finnish (NFE) AF: 0.527 AC: 575868 AN: 1093274

Other (OTH) AF: 0.483 AC: 28535 AN: 59076

GnomAD4 genome AF: 0.430 AC: 65321 AN: 152078 Hom.: 15308 Cov.: 33 AF XY: 0.430 AC XY: 31961 AN XY: 74330

African (AFR) AF: 0.231 AC: 9566 AN: 41480

American (AMR) AF: 0.450 AC: 6878 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2507 AN: 5174

South Asian (SAS) AF: 0.389 AC: 1876 AN: 4818

European-Finnish (FIN) AF: 0.563 AC: 5961 AN: 10582

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35389 AN: 67962

Other (OTH) AF: 0.451 AC: 950 AN: 2106

Alfa AF: 0.449 Hom.: 3489

Bravo AF: 0.417

Asia WGS AF: 0.444 AC: 1547 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		0.30
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: rs220131; hg19: chr21-43531848; COSMIC: COSV61160521; COSMIC: COSV61160521;