rs11911271

Variant names:

• chr21-42135381-T-C
• rs11911271
• NM_001004416.3:c.3776-2058T>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.3776-2058T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,196 control chromosomes in the GnomAD database, including 4,110 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 0.17 (4110 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3776-2058T>C		intron_variant	Intron 21 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.3776-2058T>C		intron_variant	Intron 21 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25496 AN: 152078 Hom.: 4079 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.168 AC: 25577 AN: 152196 Hom.: 4110 Cov.: 33 AF XY: 0.170 AC XY: 12636 AN XY: 74416

African (AFR) AF: 0.415 AC: 17215 AN: 41480

American (AMR) AF: 0.104 AC: 1598 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1421 AN: 5172

South Asian (SAS) AF: 0.0840 AC: 406 AN: 4834

European-Finnish (FIN) AF: 0.115 AC: 1216 AN: 10602

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0453 AC: 3078 AN: 68020

Other (OTH) AF: 0.125 AC: 263 AN: 2106

Alfa AF: 0.225 Hom.: 1408

Bravo AF: 0.178

Asia WGS AF: 0.185 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.68
PhyloP100		-0.45
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: rs11911271; hg19: chr21-43555491;