7-7714461-T-C

Variant names:

• chr7-7714461-T-C
• rs13246995
• NM_001302348.2:c.82+41008T>C

Variant summary

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

The NM_001302348.2(UMAD1):​c.82+41008T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,142 control chromosomes in the GnomAD database, including 13,147 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 (13147 hom., cov: 33)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.82+41008T>C		intron_variant	Intron 2 of 3	ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-1028+714A>G		intron_variant	Intron 2 of 7	ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.82+41008T>C		intron_variant	Intron 2 of 3		NP_001289278.1
UMAD1	NM_001302350.2	c.-24+38253T>C		intron_variant	Intron 3 of 4		NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMAD1	ENST00000682710.1	c.82+41008T>C		intron_variant	Intron 2 of 3		NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-1028+714A>G		intron_variant	Intron 2 of 7	1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61915 AN: 152024 Hom.: 13135 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.407 AC: 61965 AN: 152142 Hom.: 13147 Cov.: 33 AF XY: 0.403 AC XY: 30007 AN XY: 74372

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.443

Alfa AF: 0.274 Hom.: 696

Bravo AF: 0.399

Asia WGS AF: 0.355 AC: 1233 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46

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: rs13246995; hg19: chr7-7754092; COSMIC: COSV56189724;