rs1012997

chr7-7663948-A-C

Variant summary

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

The NM_001302348.2(UMAD1):c.-63-9361A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,134 control chromosomes in the GnomAD database, including 53,275 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 0.84 (53275 hom., cov: 31)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMAD1	NM_001302348.2	c.-63-9361A>C		intron_variant		ENST00000682710.1
RPA3	NM_002947.5	c.-758+21882T>G		intron_variant		ENST00000223129.8
UMAD1	NM_001302349.2	c.-56-9368A>C		intron_variant
UMAD1	NM_001302350.2	c.-275-9361A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPA3	ENST00000223129.8	c.-758+21882T>G		intron_variant		1	NM_002947.5	P1
UMAD1	ENST00000682710.1	c.-63-9361A>C		intron_variant			NM_001302348.2	P1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127033 AN: 152016 Hom.: 53254 Cov.: 31

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.835 AC: 127106 AN: 152134 Hom.: 53275 Cov.: 31 AF XY: 0.830 AC XY: 61758 AN XY: 74378

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.848

Alfa AF: 0.874 Hom.: 76475

Bravo AF: 0.841

Asia WGS AF: 0.776 AC: 2699 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.8
Dann	Benign	0.75

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: rs1012997; hg19: chr7-7703579;