rs6967126

Positions:

• chr7-7706459-C-A
• chr7-7706459-C-G

Variant summary

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

The NM_001302348.2(UMAD1):​c.82+33006C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,882 control chromosomes in the GnomAD database, including 12,793 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 0.41 (12793 hom., cov: 31)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.82+33006C>A		intron_variant		ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-1028+8716G>T		intron_variant		ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.82+33006C>A		intron_variant			NP_001289278.1
UMAD1	NM_001302350.2	c.-24+30251C>A		intron_variant			NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPA3	ENST00000223129.8	c.-1028+8716G>T		intron_variant		1	NM_002947.5	ENSP00000223129	P1
UMAD1	ENST00000682710.1	c.82+33006C>A		intron_variant			NM_001302348.2	ENSP00000507605	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61894 AN: 151764 Hom.: 12771 Cov.: 31

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.408 AC: 61952 AN: 151882 Hom.: 12793 Cov.: 31 AF XY: 0.405 AC XY: 30078 AN XY: 74236

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.438

Alfa AF: 0.256 Hom.: 604

Bravo AF: 0.405

Asia WGS AF: 0.347 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.52

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: rs6967126; hg19: chr7-7746090;