chr21-42106468-T-C

Variant names:

• chr21-42106468-T-C
• rs12626854
• NM_001004416.3:c.1519+2381T>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.1519+2381T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,076 control chromosomes in the GnomAD database, including 7,967 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 0.32 (7967 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• 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]

UMODL1-AS1 (HGNC:23821): (UMODL1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.1519+2381T>C		intron_variant	Intron 9 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.1519+2381T>C		intron_variant	Intron 9 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48322 AN: 151958 Hom.: 7938 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.318 AC: 48415 AN: 152076 Hom.: 7967 Cov.: 33 AF XY: 0.323 AC XY: 23989 AN XY: 74334

African (AFR) AF: 0.403 AC: 16685 AN: 41448

American (AMR) AF: 0.327 AC: 4997 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1761 AN: 5180

South Asian (SAS) AF: 0.350 AC: 1682 AN: 4812

European-Finnish (FIN) AF: 0.286 AC: 3029 AN: 10576

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18172 AN: 67988

Other (OTH) AF: 0.306 AC: 648 AN: 2116

Alfa AF: 0.299 Hom.: 925

Bravo AF: 0.325

Asia WGS AF: 0.344 AC: 1194 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.34
PhyloP100		0.24
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: rs12626854; hg19: chr21-43526578;