rs6947203

Positions:

• chr7-7697417-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+23964C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,910 control chromosomes in the GnomAD database, including 7,805 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 0.32 (7805 hom., cov: 32)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMAD1	NM_001302348.2	c.82+23964C>T		intron_variant		ENST00000682710.1
RPA3	NM_002947.5	c.-1027-10089G>A		intron_variant		ENST00000223129.8
UMAD1	NM_001302349.2	c.82+23964C>T		intron_variant
UMAD1	NM_001302350.2	c.-24+21209C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPA3	ENST00000223129.8	c.-1027-10089G>A		intron_variant		1	NM_002947.5	P1
UMAD1	ENST00000682710.1	c.82+23964C>T		intron_variant			NM_001302348.2	P1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48092 AN: 151792 Hom.: 7784 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.317 AC: 48136 AN: 151910 Hom.: 7805 Cov.: 32 AF XY: 0.317 AC XY: 23528 AN XY: 74224

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.338

Alfa AF: 0.328 Hom.: 3234

Bravo AF: 0.305

Asia WGS AF: 0.293 AC: 1017 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.17

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: rs6947203; hg19: chr7-7737048;