rs13227585

chr7-7671283-C-T

Variant summary

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

The NM_001302348.2(UMAD1):c.-63-2026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,132 control chromosomes in the GnomAD database, including 2,476 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 0.17 (2476 hom., cov: 32)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

Genes affected

UMAD1 (HGNC:48955): (UBAP1-MVB12-associated (UMA) domain containing 1)

RPA3 (HGNC:10291): (replication protein A3) Enables damaged DNA binding activity and single-stranded DNA binding activity. Involved in DNA repair and DNA replication. Part of DNA replication factor A complex. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMAD1	NM_001302348.2	c.-63-2026C>T		intron_variant		ENST00000682710.1
RPA3	NM_002947.5	c.-758+14547G>A		intron_variant		ENST00000223129.8
UMAD1	NM_001302349.2	c.-56-2033C>T		intron_variant
UMAD1	NM_001302350.2	c.-275-2026C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPA3	ENST00000223129.8	c.-758+14547G>A		intron_variant		1	NM_002947.5	P1
UMAD1	ENST00000682710.1	c.-63-2026C>T		intron_variant			NM_001302348.2	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26366 AN: 152014 Hom.: 2475 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.00942

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.173 AC: 26366 AN: 152132 Hom.: 2476 Cov.: 32 AF XY: 0.168 AC XY: 12486 AN XY: 74368

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.00925

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.193

Alfa AF: 0.206 Hom.: 4695

Bravo AF: 0.172

Asia WGS AF: 0.0800 AC: 277 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	3.6
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs13227585; hg19: chr7-7710914;