chr7-7641945-G-A

Variant names:

• chr7-7641945-G-A
• rs3757527
• NM_001302348.2:c.-64+1124G>A

Variant summary

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

The NM_001302348.2(UMAD1):​c.-64+1124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,084 control chromosomes in the GnomAD database, including 24,075 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 0.52 (24075 hom., cov: 33)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.-64+1124G>A		intron_variant	Intron 1 of 3	ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-757-770C>T		intron_variant	Intron 4 of 7	ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.-57+1124G>A		intron_variant	Intron 1 of 3		NP_001289278.1
UMAD1	NM_001302350.2	c.-276+1124G>A		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+1124G>A		intron_variant	Intron 1 of 3		NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-757-770C>T		intron_variant	Intron 4 of 7	1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79651 AN: 151966 Hom.: 24070 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.524 AC: 79676 AN: 152084 Hom.: 24075 Cov.: 33 AF XY: 0.526 AC XY: 39108 AN XY: 74350

African (AFR) AF: 0.205 AC: 8482 AN: 41438

American (AMR) AF: 0.544 AC: 8328 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2203 AN: 3472

East Asian (EAS) AF: 0.876 AC: 4539 AN: 5184

South Asian (SAS) AF: 0.698 AC: 3370 AN: 4826

European-Finnish (FIN) AF: 0.611 AC: 6452 AN: 10560

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44297 AN: 67990

Other (OTH) AF: 0.567 AC: 1197 AN: 2112

Alfa AF: 0.616 Hom.: 59526

Bravo AF: 0.502

Asia WGS AF: 0.742 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.38
PhyloP100		0.48
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: rs3757527; hg19: chr7-7681576;