dbSNP rs12702628: UMAD1:c.-64+496G>A (chr7-7641317-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001302348.2(UMAD1):c.-64+496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,022 control chromosomes in the GnomAD database, including 19,510 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 0.49 ( 19508 hom., cov: 31)

Exomes 𝑓: 0.50 ( 2 hom. )

Consequence

UMAD1
NM_001302348.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

Publications

5 publications found

Variant links:

Genes affected

UMAD1 (HGNC:48955): (UBAP1-MVB12-associated (UMA) domain containing 1)

UMAD1 links:

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]

RPA3 links:

ENSG00000283549 (HGNC:):

ENSG00000283549 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UMAD1	NM_001302348.2 link	c.-64+496G>A	intron_variant	Intron 1 of 3	ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5 link	c.-757-142C>T	intron_variant	Intron 4 of 7	ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2 link	c.-57+496G>A	intron_variant	Intron 1 of 3		NP_001289278.1
UMAD1	NM_001302350.2 link	c.-276+496G>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 link	c.-64+496G>A		intron_variant	Intron 1 of 3		NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8 link	c.-757-142C>T		intron_variant	Intron 4 of 7	1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74329

AN:

151880

Hom.:

19497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.450

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.489

AC:

74365

AN:

151998

Hom.:

19508

Cov.:

AF XY:

0.502

AC XY:

37290

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.314

AC:

13026

AN:

41442

American (AMR)

AF:

0.589

AC:

8997

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1934

AN:

3468

East Asian (EAS)

AF:

0.813

AC:

4208

AN:

5174

South Asian (SAS)

AF:

0.657

AC:

3164

AN:

4818

European-Finnish (FIN)

AF:

0.634

AC:

6676

AN:

10536

Middle Eastern (MID)

AF:

0.500

AC:

146

AN:

292

European-Non Finnish (NFE)

AF:

0.513

AC:

34864

AN:

67972

Other (OTH)

AF:

0.473

AC:

998

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1809

3619

5428

7238

9047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.512

Hom.:

10775

Bravo

AF:

0.476

Asia WGS

AF:

0.684

AC:

2381

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.5

(source)

DANN

Benign

0.88

PhyloP100

0.015

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over