rs750102975

Variant names:

• chr2-3189483-C-G
• rs750102975
• NM_003310.5:c.1015G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-3189483-C-G
• chr2-3189483-C-T
• chr2-3189483-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003310.5(EIPR1):​c.1015G>C​(p.Val339Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,415,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EIPR1 NM_003310.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

Genes affected

EIPR1 (HGNC:12383): (EARP complex and GARP complex interacting protein 1) This gene has been reported in PMID 9403053 as one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. Alignment of this gene to genomic sequence data suggests that this gene resides on chromosome 2 rather than chromosome 11. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15293336).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003310.5. 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
	EIPR1	NM_003310.5	MANE Select	c.1015G>C	p.Val339Leu	missense	Exon 9 of 9	NP_003301.1	Q53HC9
	EIPR1	NM_001330530.3		c.1096G>C	p.Val366Leu	missense	Exon 10 of 10	NP_001317459.1	A8MUM1
	EIPR1	NM_001330531.3		c.583G>C	p.Val195Leu	missense	Exon 8 of 8	NP_001317460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIPR1	ENST00000382125.9	TSL:1 MANE Select	c.1015G>C	p.Val339Leu	missense	Exon 9 of 9	ENSP00000371559.4	Q53HC9
	EIPR1	ENST00000864323.1		c.1105G>C	p.Val369Leu	missense	Exon 10 of 10	ENSP00000534382.1
	EIPR1	ENST00000398659.8	TSL:5	c.1096G>C	p.Val366Leu	missense	Exon 10 of 10	ENSP00000381652.4	A8MUM1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1415398 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 696956

African (AFR) AF: 0.00 AC: 0 AN: 32956

American (AMR) AF: 0.00 AC: 0 AN: 40294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25222

East Asian (EAS) AF: 0.00 AC: 0 AN: 38372

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082564

Other (OTH) AF: 0.0000171 AC: 1 AN: 58428

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000501 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
PhyloP100		3.0
Varity_R		0.073
gMVP		0.25
Mutation Taster		=79/21	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs750102975; hg19: chr2-3193254;