21-42126595-T-C

Variant names:

• chr21-42126595-T-C
• rs220157
• NM_001004416.3:c.3293+105T>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.3293+105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 1,517,482 control chromosomes in the GnomAD database, including 549,740 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 0.82 (51907 hom., cov: 32)
  • Exomes 𝑓: 0.85 (497833 hom.)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 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.3293+105T>C		intron	N/A	NP_001004416.3	Q5DID0-1
	UMODL1	NM_173568.4		c.3677+105T>C		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3461+105T>C		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.3293+105T>C		intron	N/A	ENSP00000386147.2	Q5DID0-1
	UMODL1	ENST00000408989.6	TSL:1	c.3677+105T>C		intron	N/A	ENSP00000386126.2	Q5DID0-2
	UMODL1	ENST00000400427.5	TSL:1	c.3461+105T>C		intron	N/A	ENSP00000383279.1	Q5DID0-4

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125300 AN: 152066 Hom.: 51861 Cov.: 32

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.829

GnomAD4 exome AF: 0.853 AC: 1163964 AN: 1365298 Hom.: 497833 AF XY: 0.852 AC XY: 575064 AN XY: 675146

African (AFR) AF: 0.760 AC: 23817 AN: 31336

American (AMR) AF: 0.826 AC: 31502 AN: 38136

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 21008 AN: 23246

East Asian (EAS) AF: 0.632 AC: 23540 AN: 37230

South Asian (SAS) AF: 0.805 AC: 61855 AN: 76854

European-Finnish (FIN) AF: 0.845 AC: 37794 AN: 44706

Middle Eastern (MID) AF: 0.898 AC: 4873 AN: 5424

European-Non Finnish (NFE) AF: 0.867 AC: 911713 AN: 1051548

Other (OTH) AF: 0.842 AC: 47862 AN: 56818

GnomAD4 genome AF: 0.824 AC: 125402 AN: 152184 Hom.: 51907 Cov.: 32 AF XY: 0.819 AC XY: 60946 AN XY: 74390

African (AFR) AF: 0.771 AC: 31997 AN: 41504

American (AMR) AF: 0.831 AC: 12706 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3124 AN: 3472

East Asian (EAS) AF: 0.614 AC: 3162 AN: 5152

South Asian (SAS) AF: 0.788 AC: 3803 AN: 4826

European-Finnish (FIN) AF: 0.840 AC: 8912 AN: 10604

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58880 AN: 68014

Other (OTH) AF: 0.829 AC: 1754 AN: 2116

Alfa AF: 0.850 Hom.: 29683

Bravo AF: 0.820

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.34
PhyloP100		-2.0
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: rs220157; hg19: chr21-43546705;