chr2-3194079-G-A

Variant names:

• chr2-3194079-G-A
• rs148363289
• NM_003310.5:c.741C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003310.5(EIPR1):​c.741C>T​(p.Cys247Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,613,922 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (10 hom.)
• Consequence: EIPR1 NM_003310.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.339
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 2-3194079-G-A is Benign according to our data. Variant chr2-3194079-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2650632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.339 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.741C>T	p.Cys247Cys	synonymous	Exon 7 of 9	NP_003301.1	Q53HC9
	EIPR1	NM_001330530.3		c.822C>T	p.Cys274Cys	synonymous	Exon 8 of 10	NP_001317459.1	A8MUM1
	EIPR1	NM_001330531.3		c.309C>T	p.Cys103Cys	synonymous	Exon 6 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.741C>T	p.Cys247Cys	synonymous	Exon 7 of 9	ENSP00000371559.4	Q53HC9
	EIPR1	ENST00000864323.1		c.831C>T	p.Cys277Cys	synonymous	Exon 8 of 10	ENSP00000534382.1
	EIPR1	ENST00000398659.8	TSL:5	c.822C>T	p.Cys274Cys	synonymous	Exon 8 of 10	ENSP00000381652.4	A8MUM1

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 414 AN: 152168 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00208 AC: 522 AN: 251292 AF XY: 0.00190

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00286

Gnomad NFE exome AF: 0.00322

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00299 AC: 4363 AN: 1461636 Hom.: 10 Cov.: 30 AF XY: 0.00287 AC XY: 2087 AN XY: 727106

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.00179 AC: 80 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00252 AC: 134 AN: 53188

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00359 AC: 3989 AN: 1111990

Other (OTH) AF: 0.00232 AC: 140 AN: 60392

GnomAD4 genome AF: 0.00272 AC: 414 AN: 152286 Hom.: 2 Cov.: 33 AF XY: 0.00240 AC XY: 179 AN XY: 74440

African (AFR) AF: 0.000794 AC: 33 AN: 41560

American (AMR) AF: 0.00431 AC: 66 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00255 AC: 27 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00366 AC: 249 AN: 68028

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00215 Hom.: 0

Bravo AF: 0.00303

EpiCase AF: 0.00327

EpiControl AF: 0.00308

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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

Other links and lift over

dbSNP: rs148363289; hg19: chr2-3197850; COSMIC: COSV66133149; COSMIC: COSV66133149;