rs12702628

Positions:

• chr7-7641317-G-A
• chr7-7641317-G-C

Variant summary

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

The NM_001302348.2(UMAD1):​c.-64+496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,022 control chromosomes in the GnomAD database, including 19,510 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 0.49 (19508 hom., cov: 31)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.-64+496G>A		intron_variant		ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-757-142C>T		intron_variant		ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.-57+496G>A		intron_variant			NP_001289278.1
UMAD1	NM_001302350.2	c.-276+496G>A		intron_variant			NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPA3	ENST00000223129.8	c.-757-142C>T		intron_variant		1	NM_002947.5	ENSP00000223129	P1
UMAD1	ENST00000682710.1	c.-64+496G>A		intron_variant			NM_001302348.2	ENSP00000507605	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74329 AN: 151880 Hom.: 19497 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.500 AC: 12 AN: 24 Hom.: 2 AF XY: 0.450 AC XY: 9 AN XY: 20

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.489 AC: 74365 AN: 151998 Hom.: 19508 Cov.: 31 AF XY: 0.502 AC XY: 37290 AN XY: 74294

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.473

Alfa AF: 0.508 Hom.: 6739

Bravo AF: 0.476

Asia WGS AF: 0.684 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.88

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: rs12702628; hg19: chr7-7680948;