7-7641389-C-T

Variant names:

• chr7-7641389-C-T
• rs7792009
• NM_001302348.2:c.-64+568C>T

Variant summary

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

The NM_001302348.2(UMAD1):​c.-64+568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,148 control chromosomes in the GnomAD database, including 6,358 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 0.25 (6350 hom., cov: 32)
  • Exomes 𝑓: 0.37 (8 hom.)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712

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]

ENSG00000283549 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.-64+568C>T		intron_variant	Intron 1 of 3	ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-757-214G>A		intron_variant	Intron 4 of 7	ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.-57+568C>T		intron_variant	Intron 1 of 3		NP_001289278.1
UMAD1	NM_001302350.2	c.-276+568C>T		intron_variant	Intron 1 of 4		NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMAD1	ENST00000682710.1	c.-64+568C>T		intron_variant	Intron 1 of 3		NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-757-214G>A		intron_variant	Intron 4 of 7	1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38096 AN: 151954 Hom.: 6341 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.368 AC: 28 AN: 76 Hom.: 8 AF XY: 0.367 AC XY: 22 AN XY: 60

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.251 AC: 38114 AN: 152072 Hom.: 6350 Cov.: 32 AF XY: 0.261 AC XY: 19402 AN XY: 74324

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.249

Alfa AF: 0.282 Hom.: 8368

Bravo AF: 0.236

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.1
DANN	Benign	0.77

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: rs7792009; hg19: chr7-7681020;