7-7643979-C-T

Variant names:

• chr7-7643979-C-T
• rs6974232
• NM_001302348.2:c.-64+3158C>T

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+3158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,862 control chromosomes in the GnomAD database, including 9,492 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 0.31 (9492 hom., cov: 31)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMAD1	NM_001302348.2	MANE Select	c.-64+3158C>T		intron	N/A	NP_001289277.1
	RPA3	NM_002947.5	MANE Select	c.-757-2804G>A		intron	N/A	NP_002938.1
	UMAD1	NM_001302349.2		c.-57+3158C>T		intron	N/A	NP_001289278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMAD1	ENST00000682710.1	MANE Select	c.-64+3158C>T		intron	N/A	ENSP00000507605.1
	RPA3	ENST00000223129.8	TSL:1 MANE Select	c.-757-2804G>A		intron	N/A	ENSP00000223129.4
	UMAD1	ENST00000949980.1		c.-64+3158C>T		intron	N/A	ENSP00000620039.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47556 AN: 151744 Hom.: 9490 Cov.: 31

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.313 AC: 47571 AN: 151862 Hom.: 9492 Cov.: 31 AF XY: 0.321 AC XY: 23780 AN XY: 74180

African (AFR) AF: 0.0839 AC: 3479 AN: 41472

American (AMR) AF: 0.336 AC: 5126 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1135 AN: 3468

East Asian (EAS) AF: 0.790 AC: 4074 AN: 5154

South Asian (SAS) AF: 0.496 AC: 2384 AN: 4806

European-Finnish (FIN) AF: 0.444 AC: 4651 AN: 10486

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25666 AN: 67930

Other (OTH) AF: 0.299 AC: 627 AN: 2096

Alfa AF: 0.304 Hom.: 1259

Bravo AF: 0.294

Asia WGS AF: 0.587 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.63
PhyloP100		-1.7
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: rs6974232; hg19: chr7-7683610;