rs2940531

chr5-176906768-A-G

Variant summary

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

The NM_001199298.2(UIMC1):c.1912+346T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,266 control chromosomes in the GnomAD database, including 3,286 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 0.14 (3286 hom., cov: 33)
• Consequence: UIMC1 NM_001199298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

Genes affected

UIMC1 (HGNC:30298): (ubiquitin interaction motif containing 1) This gene encodes a nuclear protein that interacts with Brca1 (breast cancer 1) in a complex to recognize and repair DNA lesions. This protein binds ubiquitinated lysine 63 of histone H2A and H2AX. This protein may also function as a repressor of transcription. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UIMC1	NM_001199298.2	c.1912+346T>C		intron_variant		ENST00000511320.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UIMC1	ENST00000511320.6	c.1912+346T>C		intron_variant		1	NM_001199298.2	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21504 AN: 152148 Hom.: 3262 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.142 AC: 21572 AN: 152266 Hom.: 3286 Cov.: 33 AF XY: 0.138 AC XY: 10264 AN XY: 74472

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.0854

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0412

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0856 Hom.: 341

Bravo AF: 0.155

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.93
Dann	Benign	0.49

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: rs2940531; hg19: chr5-176333769;