rs7456324

chr7-7715860-C-Achr7-7715860-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.82+42407C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.083 in 152,120 control chromosomes in the GnomAD database, including 619 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 0.083 (619 hom., cov: 32)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMAD1	NM_001302348.2	c.82+42407C>A		intron_variant		ENST00000682710.1
RPA3	NM_002947.5	c.-1079-634G>T		intron_variant		ENST00000223129.8
UMAD1	NM_001302349.2	c.82+42407C>A		intron_variant
UMAD1	NM_001302350.2	c.-24+39652C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPA3	ENST00000223129.8	c.-1079-634G>T		intron_variant		1	NM_002947.5	P1
UMAD1	ENST00000682710.1	c.82+42407C>A		intron_variant			NM_001302348.2	P1

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12607 AN: 152002 Hom.: 617 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0883

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0978

Gnomad OTH AF: 0.0771

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

GnomAD4 genome AF: 0.0830 AC: 12624 AN: 152120 Hom.: 619 Cov.: 32 AF XY: 0.0863 AC XY: 6419 AN XY: 74348

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.0952

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.0888

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.0979

Gnomad4 OTH AF: 0.0782

Alfa AF: 0.0767 Hom.: 239

Bravo AF: 0.0762

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.2
Dann	Benign	0.22

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: rs7456324; hg19: chr7-7755491;