5-66021353-C-T

Variant names:

• chr5-66021353-C-T
• rs706679
• NM_001253697.2:c.565C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001253697.2(ERBIN):​c.565C>T​(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 1,599,706 control chromosomes in the GnomAD database, including 555,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (42667 hom., cov: 32)
  • Exomes 𝑓: 0.84 (512421 hom.)
• Consequence: ERBIN NM_001253697.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.260
• Publications: 24 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 5-66021353-C-T is Benign according to our data. Variant chr5-66021353-C-T is described in ClinVar as Benign. ClinVar VariationId is 1169278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

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.565C>T	p.Leu189Leu	synonymous	Exon 8 of 26	NP_001240626.1	Q96RT1-1
	ERBIN	NM_001253699.2		c.565C>T	p.Leu189Leu	synonymous	Exon 8 of 26	NP_001240628.1	Q96RT1-8
	ERBIN	NM_018695.4		c.565C>T	p.Leu189Leu	synonymous	Exon 8 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.565C>T	p.Leu189Leu	synonymous	Exon 8 of 26	ENSP00000284037.4	Q96RT1-1
	ERBIN	ENST00000506030.6	TSL:1	c.565C>T	p.Leu189Leu	synonymous	Exon 8 of 26	ENSP00000426632.1	Q96RT1-8
	ERBIN	ENST00000380943.6	TSL:1	c.565C>T	p.Leu189Leu	synonymous	Exon 8 of 25	ENSP00000370330.2	Q96RT1-2

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111448 AN: 151746 Hom.: 42661 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.731

GnomAD2 exomes AF: 0.761 AC: 187314 AN: 246270 AF XY: 0.779

Gnomad AFR exome AF: 0.517

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.729

Gnomad EAS exome AF: 0.514

Gnomad FIN exome AF: 0.850

Gnomad NFE exome AF: 0.861

Gnomad OTH exome AF: 0.800

GnomAD4 exome AF: 0.836 AC: 1209679 AN: 1447842 Hom.: 512421 Cov.: 32 AF XY: 0.837 AC XY: 603518 AN XY: 720736

African (AFR) AF: 0.515 AC: 16952 AN: 32918

American (AMR) AF: 0.553 AC: 24338 AN: 43976

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 18915 AN: 25910

East Asian (EAS) AF: 0.547 AC: 21446 AN: 39200

South Asian (SAS) AF: 0.847 AC: 72005 AN: 85050

European-Finnish (FIN) AF: 0.850 AC: 45275 AN: 53272

Middle Eastern (MID) AF: 0.808 AC: 4047 AN: 5010

European-Non Finnish (NFE) AF: 0.869 AC: 958406 AN: 1102654

Other (OTH) AF: 0.807 AC: 48295 AN: 59852

GnomAD4 genome AF: 0.734 AC: 111471 AN: 151864 Hom.: 42667 Cov.: 32 AF XY: 0.732 AC XY: 54326 AN XY: 74214

African (AFR) AF: 0.534 AC: 22092 AN: 41382

American (AMR) AF: 0.658 AC: 10042 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2526 AN: 3466

East Asian (EAS) AF: 0.541 AC: 2797 AN: 5174

South Asian (SAS) AF: 0.842 AC: 4057 AN: 4820

European-Finnish (FIN) AF: 0.851 AC: 9005 AN: 10576

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58434 AN: 67886

Other (OTH) AF: 0.732 AC: 1541 AN: 2106

Alfa AF: 0.795 Hom.: 34936

Bravo AF: 0.706

Asia WGS AF: 0.723 AC: 2515 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.4
DANN	Benign	0.75
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs706679; hg19: chr5-65317181; COSMIC: COSV52317034; COSMIC: COSV52317034;