chr21-42116792-G-C

Variant names:

• chr21-42116792-G-C
• rs220140
• NM_001004416.3:c.2475+807G>C

Variant summary

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

The NM_173568.4(UMODL1):​c.2859+807G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,048 control chromosomes in the GnomAD database, including 28,206 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 0.61 (28206 hom., cov: 33)
• Consequence: UMODL1 NM_173568.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173568.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	NM_001004416.3	MANE Select	c.2475+807G>C		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.2859+807G>C		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.2643+807G>C		intron	N/A	NP_001186456.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.2475+807G>C		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.2859+807G>C		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.2643+807G>C		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92488 AN: 151930 Hom.: 28179 Cov.: 33

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.609 AC: 92562 AN: 152048 Hom.: 28206 Cov.: 33 AF XY: 0.609 AC XY: 45303 AN XY: 74342

African (AFR) AF: 0.582 AC: 24111 AN: 41462

American (AMR) AF: 0.674 AC: 10307 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2235 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3396 AN: 5176

South Asian (SAS) AF: 0.669 AC: 3224 AN: 4822

European-Finnish (FIN) AF: 0.584 AC: 6154 AN: 10544

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40987 AN: 67962

Other (OTH) AF: 0.602 AC: 1272 AN: 2114

Alfa AF: 0.446 Hom.: 1135

Bravo AF: 0.616

Asia WGS AF: 0.652 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.29
PhyloP100		-0.22
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: rs220140; hg19: chr21-43536902;