rs2305491

Positions:

• chr2-3194404-C-T

Variant summary

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

The NM_003310.5(EIPR1):​c.654-238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 367,636 control chromosomes in the GnomAD database, including 138,235 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 0.86 (56580 hom., cov: 30)
  • Exomes 𝑓: 0.86 (81655 hom.)
• Consequence: EIPR1 NM_003310.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446

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

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 = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIPR1	NM_003310.5	c.654-238G>A		intron_variant		ENST00000382125.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIPR1	ENST00000382125.9	c.654-238G>A		intron_variant		1	NM_003310.5	P1

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130454 AN: 151932 Hom.: 56544 Cov.: 30

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.876

GnomAD4 exome AF: 0.863 AC: 186028 AN: 215586 Hom.: 81655 Cov.: 4 AF XY: 0.863 AC XY: 94931 AN XY: 109948

Gnomad4 AFR exome AF: 0.813

Gnomad4 AMR exome AF: 0.900

Gnomad4 ASJ exome AF: 0.930

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.780

Gnomad4 FIN exome AF: 0.869

Gnomad4 NFE exome AF: 0.911

Gnomad4 OTH exome AF: 0.866

GnomAD4 genome AF: 0.859 AC: 130551 AN: 152050 Hom.: 56580 Cov.: 30 AF XY: 0.854 AC XY: 63493 AN XY: 74320

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.930

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.877

Alfa AF: 0.896 Hom.: 32268

Bravo AF: 0.860

Asia WGS AF: 0.633 AC: 2206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.64

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: rs2305491; hg19: chr2-3198175;