Genetic Variant 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UMAD1	NM_001302348.2	MANE Select	c.-64+496G>A	intron	N/A	NP_001289277.1	C9J7I0
RPA3	NM_002947.5	MANE Select	c.-757-142C>T	intron	N/A	NP_002938.1	P35244
UMAD1	NM_001302349.2		c.-57+496G>A	intron	N/A	NP_001289278.1	C9J7I0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UMAD1	ENST00000682710.1	MANE Select	c.-64+496G>A	intron	N/A	ENSP00000507605.1	C9J7I0
RPA3	ENST00000223129.8	TSL:1 MANE Select	c.-757-142C>T	intron	N/A	ENSP00000223129.4	P35244
UMAD1	ENST00000949981.1		c.-452G>A	5_prime_UTR	Exon 1 of 4	ENSP00000620040.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over