rs3764211

Variant names:

• chr15-29151746-A-G
• rs3764211
• NM_015307.2:c.618T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015307.2(ENTREP2):​c.618T>C​(p.Asp206Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,551,226 control chromosomes in the GnomAD database, including 8,548 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 0.15 (3112 hom., cov: 33)
  • Exomes 𝑓: 0.067 (5436 hom.)
• Consequence: ENTREP2 NM_015307.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 9 publications found

Genes affected

ENTREP2 (HGNC:29075): (endosomal transmembrane epsin interactor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.258 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015307.2. 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
	ENTREP2	NM_015307.2	MANE Select	c.618T>C	p.Asp206Asp	synonymous	Exon 5 of 11	NP_056122.1	O60320-1
	ENTREP2	NM_001387214.1		c.483T>C	p.Asp161Asp	synonymous	Exon 4 of 10	NP_001374143.1
	ENTREP2	NM_001387215.1		c.330T>C	p.Asp110Asp	synonymous	Exon 5 of 12	NP_001374144.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTREP2	ENST00000261275.5	TSL:5 MANE Select	c.618T>C	p.Asp206Asp	synonymous	Exon 5 of 11	ENSP00000261275.4	O60320-1
	ENTREP2	ENST00000560021.1	TSL:1	n.354T>C		non_coding_transcript_exon	Exon 2 of 8
	ENTREP2	ENST00000918355.1		c.846T>C	p.Asp282Asp	synonymous	Exon 6 of 13	ENSP00000588414.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22600 AN: 152054 Hom.: 3099 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.140

GnomAD2 exomes AF: 0.0931 AC: 14680 AN: 157630 AF XY: 0.0859

Gnomad AFR exome AF: 0.369

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.0315

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.0396

Gnomad NFE exome AF: 0.0499

Gnomad OTH exome AF: 0.0836

GnomAD4 exome AF: 0.0671 AC: 93823 AN: 1399054 Hom.: 5436 Cov.: 31 AF XY: 0.0661 AC XY: 45632 AN XY: 690028

African (AFR) AF: 0.376 AC: 11873 AN: 31560

American (AMR) AF: 0.138 AC: 4932 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.0344 AC: 866 AN: 25180

East Asian (EAS) AF: 0.177 AC: 6332 AN: 35736

South Asian (SAS) AF: 0.0774 AC: 6129 AN: 79222

European-Finnish (FIN) AF: 0.0413 AC: 2031 AN: 49198

Middle Eastern (MID) AF: 0.0674 AC: 384 AN: 5696

European-Non Finnish (NFE) AF: 0.0520 AC: 56111 AN: 1078666

Other (OTH) AF: 0.0889 AC: 5165 AN: 58094

GnomAD4 genome AF: 0.149 AC: 22656 AN: 152172 Hom.: 3112 Cov.: 33 AF XY: 0.146 AC XY: 10866 AN XY: 74398

African (AFR) AF: 0.363 AC: 15066 AN: 41468

American (AMR) AF: 0.119 AC: 1812 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 114 AN: 3472

East Asian (EAS) AF: 0.178 AC: 919 AN: 5162

South Asian (SAS) AF: 0.0902 AC: 435 AN: 4822

European-Finnish (FIN) AF: 0.0419 AC: 445 AN: 10622

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0505 AC: 3432 AN: 68016

Other (OTH) AF: 0.144 AC: 305 AN: 2116

Alfa AF: 0.0847 Hom.: 1667

Bravo AF: 0.170

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		0.26
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: rs3764211; hg19: chr15-29443949; COSMIC: COSV54265467;