chr7-7687470-G-T

Position:

• chr7-7687470-G-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+14017G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,056 control chromosomes in the GnomAD database, including 25,282 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 0.57 (25270 hom., cov: 31)
  • Exomes 𝑓: 0.61 (12 hom.)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.82+14017G>T		intron_variant		ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-1027-142C>A		intron_variant		ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.82+14017G>T		intron_variant			NP_001289278.1
UMAD1	NM_001302350.2	c.-24+11262G>T		intron_variant			NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMAD1	ENST00000682710.1	c.82+14017G>T		intron_variant			NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-1027-142C>A		intron_variant		1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87178 AN: 151882 Hom.: 25256 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.607 AC: 34 AN: 56 Hom.: 12 AF XY: 0.568 AC XY: 25 AN XY: 44

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.574 AC: 87225 AN: 152000 Hom.: 25270 Cov.: 31 AF XY: 0.577 AC XY: 42849 AN XY: 74318

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.546

Alfa AF: 0.555 Hom.: 8720

Bravo AF: 0.577

Asia WGS AF: 0.630 AC: 2193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.2
DANN	Benign	0.79

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: rs4140805; hg19: chr7-7727101;