21-42065970-A-C

Position:

• chr21-42065970-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000400427.5(UMODL1):​c.-141+2756A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,114 control chromosomes in the GnomAD database, including 1,970 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 0.15 (1970 hom., cov: 31)
• Consequence: UMODL1 ENST00000400427.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

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

Verdict is Benign. Variant got -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 = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001199527.3	c.-141+2756A>C		intron_variant
UMODL1	NM_001199528.4	c.-141+2756A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000400424.6	c.-141+2756A>C		intron_variant		1		A2
UMODL1	ENST00000400427.5	c.-141+2756A>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22048 AN: 151996 Hom.: 1967 Cov.: 31

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.145 AC: 22079 AN: 152114 Hom.: 1970 Cov.: 31 AF XY: 0.144 AC XY: 10743 AN XY: 74370

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.142

Alfa AF: 0.101 Hom.: 1156

Bravo AF: 0.155

Asia WGS AF: 0.144 AC: 503 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	0.83
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13340012; hg19: chr21-43486079;