9-69385787-TAA-TA

Variant names:

• chr9-69385787-TA-T
• rs193921010
• NM_001347995.2:c.1163-5delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001347995.2(ENTREP1):​c.1163-5delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 934,706 control chromosomes in the GnomAD database, including 1,826 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (238 hom., cov: 0)
  • Exomes 𝑓: 0.035 (1588 hom.)
• Consequence: ENTREP1 NM_001347995.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: -1.11
• Publications: 0 publications found

Genes affected

ENTREP1 (HGNC:24820): (endosomal transmembrane epsin interactor 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTREP1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-69385787-TA-T is Benign according to our data. Variant chr9-69385787-TA-T is described in ClinVar as Benign. ClinVar VariationId is 161521.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347995.2. 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
	ENTREP1	NM_001347995.2	MANE Select	c.1163-5delA		splice_region intron	N/A	NP_001334924.1	Q15884-4
	ENTREP1	NM_001127608.3		c.704-5delA		splice_region intron	N/A	NP_001121080.1	Q15884-3
	ENTREP1	NM_004816.5		c.704-5delA		splice_region intron	N/A	NP_004807.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTREP1	ENST00000303068.14	TSL:2 MANE Select	c.1163-5delA		splice_region intron	N/A	ENSP00000304435.8	Q15884-4
	ENTREP1	ENST00000257515.12	TSL:1	c.704-5delA		splice_region intron	N/A	ENSP00000257515.8	Q15884-3
	ENTREP1	ENST00000377216.4	TSL:1	n.*381-5delA		splice_region intron	N/A	ENSP00000366422.4	A0A0A0MRU1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 4664 AN: 51782 Hom.: 239 Cov.: 0

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0897

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.0859

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0905

GnomAD2 exomes AF: 0.122 AC: 5020 AN: 41060 AF XY: 0.113

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0603

Gnomad ASJ exome AF: 0.0681

Gnomad EAS exome AF: 0.0600

Gnomad FIN exome AF: 0.219

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.0844

GnomAD4 exome AF: 0.0350 AC: 30931 AN: 882894 Hom.: 1588 Cov.: 34 AF XY: 0.0366 AC XY: 15509 AN XY: 423402

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0655 AC: 1031 AN: 15736

American (AMR) AF: 0.0472 AC: 423 AN: 8962

Ashkenazi Jewish (ASJ) AF: 0.0485 AC: 524 AN: 10808

East Asian (EAS) AF: 0.0342 AC: 568 AN: 16598

South Asian (SAS) AF: 0.0843 AC: 2973 AN: 35286

European-Finnish (FIN) AF: 0.135 AC: 3291 AN: 24468

Middle Eastern (MID) AF: 0.0460 AC: 107 AN: 2326

European-Non Finnish (NFE) AF: 0.0282 AC: 20770 AN: 735718

Other (OTH) AF: 0.0377 AC: 1244 AN: 32992

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0902 AC: 4673 AN: 51812 Hom.: 238 Cov.: 0 AF XY: 0.0928 AC XY: 2303 AN XY: 24810

African (AFR) AF: 0.188 AC: 2194 AN: 11696

American (AMR) AF: 0.0498 AC: 260 AN: 5224

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 119 AN: 1454

East Asian (EAS) AF: 0.0334 AC: 77 AN: 2306

South Asian (SAS) AF: 0.0752 AC: 106 AN: 1410

European-Finnish (FIN) AF: 0.0678 AC: 187 AN: 2760

Middle Eastern (MID) AF: 0.0948 AC: 11 AN: 116

European-Non Finnish (NFE) AF: 0.0629 AC: 1615 AN: 25692

Other (OTH) AF: 0.0904 AC: 64 AN: 708

Alfa AF: 0.000993 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
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: rs193921010; hg19: chr9-72000703; COSMIC: COSV99974734;