rs2057931

Positions:

• chr7-7670110-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.-63-3199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,986 control chromosomes in the GnomAD database, including 25,916 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 0.58 (25916 hom., cov: 32)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.-63-3199C>T		intron_variant		ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-758+15720G>A		intron_variant		ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.-56-3206C>T		intron_variant			NP_001289278.1
UMAD1	NM_001302350.2	c.-275-3199C>T		intron_variant			NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPA3	ENST00000223129.8	c.-758+15720G>A		intron_variant		1	NM_002947.5	ENSP00000223129	P1
UMAD1	ENST00000682710.1	c.-63-3199C>T		intron_variant			NM_001302348.2	ENSP00000507605	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88260 AN: 151868 Hom.: 25899 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.581 AC: 88312 AN: 151986 Hom.: 25916 Cov.: 32 AF XY: 0.584 AC XY: 43382 AN XY: 74288

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.549

Alfa AF: 0.591 Hom.: 3319

Bravo AF: 0.583

Asia WGS AF: 0.628 AC: 2186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.95
DANN	Benign	0.55

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: rs2057931; hg19: chr7-7709741;