7-7652852-G-T

Position:

• chr7-7652852-G-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+12031G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,126 control chromosomes in the GnomAD database, including 10,015 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 0.34 (10015 hom., cov: 33)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.9).
• 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	UniProt
UMAD1	NM_001302348.2	c.-64+12031G>T		intron_variant		ENST00000682710.1
RPA3	NM_002947.5	c.-757-11677C>A		intron_variant		ENST00000223129.8
UMAD1	NM_001302349.2	c.-57+12031G>T		intron_variant
UMAD1	NM_001302350.2	c.-276+12031G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPA3	ENST00000223129.8	c.-757-11677C>A		intron_variant		1	NM_002947.5	P1
UMAD1	ENST00000682710.1	c.-64+12031G>T		intron_variant			NM_001302348.2	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52373 AN: 152008 Hom.: 10008 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.344 AC: 52402 AN: 152126 Hom.: 10015 Cov.: 33 AF XY: 0.352 AC XY: 26171 AN XY: 74374

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.325

Alfa AF: 0.357 Hom.: 12908

Bravo AF: 0.330

Asia WGS AF: 0.589 AC: 2047 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.74

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: rs886724; hg19: chr7-7692483; COSMIC: COSV56189717;