21-42124950-A-G

Variant names:

• chr21-42124950-A-G
• rs11910495
• NM_001004416.3:c.3148-1395A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004416.3(UMODL1):​c.3148-1395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,946 control chromosomes in the GnomAD database, including 14,943 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 0.43 (14943 hom., cov: 31)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3148-1395A>G		intron_variant	Intron 17 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.3148-1395A>G		intron_variant	Intron 17 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64969 AN: 151828 Hom.: 14946 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.428 AC: 64980 AN: 151946 Hom.: 14943 Cov.: 31 AF XY: 0.422 AC XY: 31327 AN XY: 74276

African (AFR) AF: 0.273 AC: 11315 AN: 41436

American (AMR) AF: 0.407 AC: 6209 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1813 AN: 3466

East Asian (EAS) AF: 0.191 AC: 981 AN: 5138

South Asian (SAS) AF: 0.443 AC: 2131 AN: 4814

European-Finnish (FIN) AF: 0.475 AC: 5020 AN: 10562

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36001 AN: 67942

Other (OTH) AF: 0.428 AC: 904 AN: 2110

Alfa AF: 0.500 Hom.: 11522

Bravo AF: 0.412

Asia WGS AF: 0.357 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.53
PhyloP100		-0.16
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: rs11910495; hg19: chr21-43545060;