9-69385787-TAA-TAAA

Variant names:

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

Variant summary

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

The NM_001347995.2(ENTREP1):​c.1163-5dupA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 946,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ENTREP1 NM_001347995.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1163-5dupA		splice_region intron	N/A	NP_001334924.1	Q15884-4
	ENTREP1	NM_001127608.3		c.704-5dupA		splice_region intron	N/A	NP_001121080.1	Q15884-3
	ENTREP1	NM_004816.5		c.704-5dupA		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.1163-5dupA		splice_region intron	N/A	ENSP00000304435.8	Q15884-4
	ENTREP1	ENST00000257515.12	TSL:1	c.704-5dupA		splice_region intron	N/A	ENSP00000257515.8	Q15884-3
	ENTREP1	ENST00000377216.4	TSL:1	n.*381-5dupA		splice_region intron	N/A	ENSP00000366422.4	A0A0A0MRU1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000211 AC: 2 AN: 946234 Hom.: 0 Cov.: 34 AF XY: 0.00000221 AC XY: 1 AN XY: 453218

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

African (AFR) AF: 0.00 AC: 0 AN: 17180

American (AMR) AF: 0.00 AC: 0 AN: 9130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11268

East Asian (EAS) AF: 0.00 AC: 0 AN: 17044

South Asian (SAS) AF: 0.00 AC: 0 AN: 37370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25036

Middle Eastern (MID) AF: 0.000406 AC: 1 AN: 2464

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 791680

Other (OTH) AF: 0.0000285 AC: 1 AN: 35062

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 4

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;