rs3757527

Positions:

• chr7-7641945-G-A
• chr7-7641945-G-C
• chr7-7641945-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+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

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 = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.-64+1124G>A		intron_variant		ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-757-770C>T		intron_variant		ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.-57+1124G>A		intron_variant			NP_001289278.1
UMAD1	NM_001302350.2	c.-276+1124G>A		intron_variant			NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPA3	ENST00000223129.8	c.-757-770C>T		intron_variant		1	NM_002947.5	ENSP00000223129	P1
UMAD1	ENST00000682710.1	c.-64+1124G>A		intron_variant			NM_001302348.2	ENSP00000507605	P1

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

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.567

Alfa AF: 0.626 Hom.: 44151

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

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: rs3757527; hg19: chr7-7681576;