21-42102540-C-T

Variant names:

• chr21-42102540-C-T
• rs220110
• ENST00000329015.2:n.1735G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000329015.2(UMODL1-AS1):​n.1735G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 86,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: UMODL1-AS1 ENST00000329015.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 10 publications found

Genes affected

UMODL1-AS1 (HGNC:23821): (UMODL1 antisense RNA 1)

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000329015.2. 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.1299+262C>T		intron	N/A	NP_001004416.3
	UMODL1-AS1	NR_027243.1		n.1735G>A		non_coding_transcript_exon	Exon 2 of 2
	UMODL1	NM_173568.4		c.1299+262C>T		intron	N/A	NP_775839.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1-AS1	ENST00000329015.2	TSL:1	n.1735G>A		non_coding_transcript_exon	Exon 2 of 2
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.1299+262C>T		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.1299+262C>T		intron	N/A	ENSP00000386126.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000116 AC: 1 AN: 86216 Hom.: 0 Cov.: 0 AF XY: 0.0000227 AC XY: 1 AN XY: 44124

African (AFR) AF: 0.000312 AC: 1 AN: 3202

American (AMR) AF: 0.00 AC: 0 AN: 3022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3610

East Asian (EAS) AF: 0.00 AC: 0 AN: 7126

South Asian (SAS) AF: 0.00 AC: 0 AN: 3108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 452

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54960

Other (OTH) AF: 0.00 AC: 0 AN: 6036

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.72
DANN	Benign	0.82
PhyloP100		0.25

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: rs220110; hg19: chr21-43522650;