7-7648195-T-G

Position:

• chr7-7648195-T-G

Variant summary

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

The NM_001302348.2(UMAD1):​c.-64+7374T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,990 control chromosomes in the GnomAD database, including 34,195 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 0.67 (34195 hom., cov: 31)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.-64+7374T>G		intron_variant		ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-757-7020A>C		intron_variant		ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.-57+7374T>G		intron_variant			NP_001289278.1
UMAD1	NM_001302350.2	c.-276+7374T>G		intron_variant			NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMAD1	ENST00000682710.1	c.-64+7374T>G		intron_variant			NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-757-7020A>C		intron_variant		1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101151 AN: 151868 Hom.: 34168 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.666 AC: 101234 AN: 151990 Hom.: 34195 Cov.: 31 AF XY: 0.673 AC XY: 49991 AN XY: 74270

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.607

Alfa AF: 0.611 Hom.: 57229

Bravo AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.73

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: rs1859604; hg19: chr7-7687826; COSMIC: COSV56189277;