chr21-42092214-G-A

Variant names:

• chr21-42092214-G-A
• rs2839466
• NM_001004416.3:c.931+1776G>A

Variant summary

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

The NM_001004416.3(UMODL1):​c.931+1776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,994 control chromosomes in the GnomAD database, including 3,838 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 0.22 (3838 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004416.3. 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.931+1776G>A		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.931+1776G>A		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.715+1776G>A		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.931+1776G>A		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.931+1776G>A		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.715+1776G>A		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33243 AN: 151876 Hom.: 3836 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.219 AC: 33266 AN: 151994 Hom.: 3838 Cov.: 32 AF XY: 0.225 AC XY: 16721 AN XY: 74258

African (AFR) AF: 0.195 AC: 8076 AN: 41456

American (AMR) AF: 0.260 AC: 3980 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3468

East Asian (EAS) AF: 0.358 AC: 1843 AN: 5152

South Asian (SAS) AF: 0.332 AC: 1598 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2706 AN: 10544

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13746 AN: 67962

Other (OTH) AF: 0.190 AC: 399 AN: 2104

Alfa AF: 0.217 Hom.: 1182

Bravo AF: 0.218

Asia WGS AF: 0.342 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.17
PhyloP100		-0.30
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: rs2839466; hg19: chr21-43512324;