rs2940531

Variant names:

• chr5-176906768-A-G
• rs2940531
• NM_001199298.2:c.1912+346T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

UIMC1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000298307 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UIMC1	NM_001199298.2	c.1912+346T>C		intron_variant	Intron 13 of 14	ENST00000511320.6	NP_001186227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UIMC1	ENST00000511320.6	c.1912+346T>C		intron_variant	Intron 13 of 14	1	NM_001199298.2	ENSP00000421926.1
UIMC1	ENST00000506128.5	c.1414+346T>C		intron_variant	Intron 13 of 14	1		ENSP00000427480.1

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

African (AFR) AF: 0.379 AC: 15741 AN: 41504

American (AMR) AF: 0.0854 AC: 1306 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3470

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5190

South Asian (SAS) AF: 0.132 AC: 636 AN: 4832

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10622

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.0412 AC: 2805 AN: 68028

Other (OTH) AF: 0.134 AC: 283 AN: 2114

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
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2940531; hg19: chr5-176333769;