5-66054546-A-T

Variant names:

• chr5-66054546-A-T
• rs36303
• NM_001253697.2:c.3228A>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001253697.2(ERBIN):​c.3228A>T​(p.Arg1076Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1076R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERBIN NM_001253697.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.995
• Publications: 21 publications found

Genes affected

ERBIN (HGNC:15842): (erbb2 interacting protein) This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ERBIN Gene-Disease associations (from GenCC):

• autosomal dominant combined immunodeficiency due to ERBIN deficiency

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.995 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253697.2. 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
	ERBIN	NM_001253697.2	MANE Select	c.3228A>T	p.Arg1076Arg	synonymous	Exon 21 of 26	NP_001240626.1	Q96RT1-1
	ERBIN	NM_001253699.2		c.3228A>T	p.Arg1076Arg	synonymous	Exon 21 of 26	NP_001240628.1	Q96RT1-8
	ERBIN	NM_018695.4		c.3228A>T	p.Arg1076Arg	synonymous	Exon 21 of 25	NP_061165.1	Q96RT1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERBIN	ENST00000284037.10	TSL:1 MANE Select	c.3228A>T	p.Arg1076Arg	synonymous	Exon 21 of 26	ENSP00000284037.4	Q96RT1-1
	ERBIN	ENST00000506030.6	TSL:1	c.3228A>T	p.Arg1076Arg	synonymous	Exon 21 of 26	ENSP00000426632.1	Q96RT1-8
	ERBIN	ENST00000380943.6	TSL:1	c.3228A>T	p.Arg1076Arg	synonymous	Exon 21 of 25	ENSP00000370330.2	Q96RT1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.3
DANN	Benign	0.63
PhyloP100		0.99
PromoterAI		-0.0042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs36303; hg19: chr5-65350374;