7-7691051-T-C

Variant names:

• chr7-7691051-T-C
• rs6966464
• NM_001302348.2:c.82+17598T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302348.2(UMAD1):​c.82+17598T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,050 control chromosomes in the GnomAD database, including 33,547 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 0.66 (33547 hom., cov: 32)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.82+17598T>C		intron_variant	Intron 2 of 3	ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-1027-3723A>G		intron_variant	Intron 2 of 7	ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.82+17598T>C		intron_variant	Intron 2 of 3		NP_001289278.1
UMAD1	NM_001302350.2	c.-24+14843T>C		intron_variant	Intron 3 of 4		NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMAD1	ENST00000682710.1	c.82+17598T>C		intron_variant	Intron 2 of 3		NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-1027-3723A>G		intron_variant	Intron 2 of 7	1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100770 AN: 151932 Hom.: 33517 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.663 AC: 100838 AN: 152050 Hom.: 33547 Cov.: 32 AF XY: 0.663 AC XY: 49278 AN XY: 74292

African (AFR) AF: 0.663 AC: 27485 AN: 41478

American (AMR) AF: 0.688 AC: 10512 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2346 AN: 3470

East Asian (EAS) AF: 0.867 AC: 4496 AN: 5184

South Asian (SAS) AF: 0.633 AC: 3049 AN: 4818

European-Finnish (FIN) AF: 0.631 AC: 6651 AN: 10544

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44329 AN: 67960

Other (OTH) AF: 0.647 AC: 1368 AN: 2114

Alfa AF: 0.668 Hom.: 4228

Bravo AF: 0.672

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	10
DANN	Benign	0.52
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6966464; hg19: chr7-7730682;