5-176931064-A-G

Variant names:

• chr5-176931064-A-G
• rs7718874
• NM_001199298.2:c.1597+12271T>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.1597+12271T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,046 control chromosomes in the GnomAD database, including 27,060 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 0.58 (27060 hom., cov: 32)
• Consequence: UIMC1 NM_001199298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199298.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UIMC1	NM_001199298.2	MANE Select	c.1597+12271T>C		intron	N/A	NP_001186227.1	Q96RL1-1
	UIMC1	NM_001199297.2		c.1597+12271T>C		intron	N/A	NP_001186226.1	Q96RL1-1
	UIMC1	NM_016290.4		c.1597+12271T>C		intron	N/A	NP_057374.3	Q96RL1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UIMC1	ENST00000511320.6	TSL:1 MANE Select	c.1597+12271T>C		intron	N/A	ENSP00000421926.1	Q96RL1-1
	UIMC1	ENST00000377227.8	TSL:1	c.1597+12271T>C		intron	N/A	ENSP00000366434.4	Q96RL1-1
	UIMC1	ENST00000506128.5	TSL:1	c.1099+12271T>C		intron	N/A	ENSP00000427480.1	Q96RL1-2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87658 AN: 151928 Hom.: 27007 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.577 AC: 87767 AN: 152046 Hom.: 27060 Cov.: 32 AF XY: 0.573 AC XY: 42618 AN XY: 74326

African (AFR) AF: 0.811 AC: 33630 AN: 41482

American (AMR) AF: 0.424 AC: 6485 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1843 AN: 3466

East Asian (EAS) AF: 0.490 AC: 2536 AN: 5172

South Asian (SAS) AF: 0.502 AC: 2418 AN: 4820

European-Finnish (FIN) AF: 0.498 AC: 5256 AN: 10544

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33756 AN: 67968

Other (OTH) AF: 0.544 AC: 1149 AN: 2112

Alfa AF: 0.538 Hom.: 21158

Bravo AF: 0.580

Asia WGS AF: 0.544 AC: 1890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.71
PhyloP100		-1.9
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: rs7718874; hg19: chr5-176358065;