chr2-211671010-A-G

Position:

• chr2-211671010-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005235.3(ERBB4):​c.1716+2154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,992 control chromosomes in the GnomAD database, including 10,996 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 0.36 (10996 hom., cov: 32)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

Genes affected

ERBB4 (HGNC:3432): (erb-b2 receptor tyrosine kinase 4) This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.1716+2154T>C		intron_variant		ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.1716+2154T>C		intron_variant		1	NM_005235.3	ENSP00000342235	P4
ERBB4	ENST00000436443.5	c.1716+2154T>C		intron_variant		1		ENSP00000403204	A1
ERBB4	ENST00000484594.5	n.1768+2154T>C		intron_variant, non_coding_transcript_variant		1
ERBB4	ENST00000260943.11	c.1716+2154T>C		intron_variant		5		ENSP00000260943

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55221 AN: 151874 Hom.: 11002 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.391

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.363 AC: 55218 AN: 151992 Hom.: 10996 Cov.: 32 AF XY: 0.357 AC XY: 26535 AN XY: 74280

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.386

Alfa AF: 0.421 Hom.: 6064

Bravo AF: 0.356

Asia WGS AF: 0.140 AC: 491 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.3
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs1851169; hg19: chr2-212535735;