rs12627387

Variant names:

• chr21-42062817-G-A
• rs12627387
• ENST00000400427.5:c.-538G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-42062817-G-A
• chr21-42062817-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199527.3(UMODL1):​c.-538G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,256 control chromosomes in the GnomAD database, including 6,908 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 0.28 (6903 hom., cov: 33)
  • Exomes 𝑓: 0.22 (5 hom.)
• Consequence: UMODL1 NM_001199527.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001199527.3	c.-538G>A		upstream_gene_variant			NP_001186456.2
UMODL1	NM_001199528.4	c.-538G>A		upstream_gene_variant			NP_001186457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000400427.5	c.-538G>A		upstream_gene_variant		1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.-538G>A		upstream_gene_variant		1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41813 AN: 151988 Hom.: 6878 Cov.: 33

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.220 AC: 33 AN: 150 Hom.: 5 AF XY: 0.190 AC XY: 24 AN XY: 126

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.275 AC: 41897 AN: 152106 Hom.: 6903 Cov.: 33 AF XY: 0.276 AC XY: 20548 AN XY: 74360

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.272

Alfa AF: 0.0469 Hom.: 46

Bravo AF: 0.291

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12627387; hg19: chr21-43482926;