rs8133951

Variant names:

• chr21-42082756-G-A
• rs8133951
• NM_001004416.3:c.320-1328G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-42082756-G-A
• chr21-42082756-G-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.320-1328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,164 control chromosomes in the GnomAD database, including 8,191 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 0.30 (8191 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.93
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.320-1328G>A		intron_variant	Intron 2 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.320-1328G>A		intron_variant	Intron 2 of 22	1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.320-1328G>A		intron_variant	Intron 2 of 21	1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.104-1328G>A		intron_variant	Intron 2 of 21	1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.104-1328G>A		intron_variant	Intron 2 of 22	1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46055 AN: 152046 Hom.: 8187 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.303 AC: 46071 AN: 152164 Hom.: 8191 Cov.: 33 AF XY: 0.307 AC XY: 22843 AN XY: 74390

African (AFR) AF: 0.106 AC: 4393 AN: 41524

American (AMR) AF: 0.356 AC: 5442 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 973 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1807 AN: 5176

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4818

European-Finnish (FIN) AF: 0.411 AC: 4354 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26303 AN: 67972

Other (OTH) AF: 0.305 AC: 644 AN: 2114

Alfa AF: 0.343 Hom.: 12291

Bravo AF: 0.291

Asia WGS AF: 0.348 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.059
DANN	Benign	0.65
PhyloP100		-3.9
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: rs8133951; hg19: chr21-43502866;