rs4140804

Positions:

• chr7-7674679-C-A
• chr7-7674679-C-G
• chr7-7674679-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302348.2(UMAD1):​c.82+1226C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,888 control chromosomes in the GnomAD database, including 25,612 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 0.58 (25612 hom., cov: 31)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.82+1226C>A		intron_variant		ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-758+11151G>T		intron_variant		ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.82+1226C>A		intron_variant			NP_001289278.1
UMAD1	NM_001302350.2	c.-131+1226C>A		intron_variant			NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMAD1	ENST00000682710.1	c.82+1226C>A		intron_variant			NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-758+11151G>T		intron_variant		1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87760 AN: 151770 Hom.: 25595 Cov.: 31

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.578 AC: 87812 AN: 151888 Hom.: 25612 Cov.: 31 AF XY: 0.582 AC XY: 43172 AN XY: 74230

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.545

Alfa AF: 0.577 Hom.: 5600

Bravo AF: 0.581

Asia WGS AF: 0.629 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.76

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: rs4140804; hg19: chr7-7714310;