NM_005235.3:c.*5329A>G

Variant names:

• chr2-211378286-T-C
• rs16845990
• NM_005235.3:c.*5329A>G

Variant summary

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

The NM_005235.3(ERBB4):​c.*5329A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 232,502 control chromosomes in the GnomAD database, including 18,313 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 0.39 (12007 hom., cov: 32)
  • Exomes 𝑓: 0.39 (6306 hom.)
• Consequence: ERBB4 NM_005235.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.*5329A>G		3_prime_UTR_variant	Exon 28 of 28	ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788	c.*5329A>G		3_prime_UTR_variant	Exon 28 of 28	1	NM_005235.3	ENSP00000342235.4
ERBB4	ENST00000436443	c.*5329A>G		3_prime_UTR_variant	Exon 27 of 27	1		ENSP00000403204.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59489 AN: 151834 Hom.: 11979 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.390 AC: 31445 AN: 80550 Hom.: 6306 Cov.: 0 AF XY: 0.388 AC XY: 14402 AN XY: 37082

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.392 AC: 59568 AN: 151952 Hom.: 12007 Cov.: 32 AF XY: 0.395 AC XY: 29317 AN XY: 74250

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.372

Alfa AF: 0.365 Hom.: 10028

Bravo AF: 0.398

Asia WGS AF: 0.505 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.70

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: rs16845990; hg19: chr2-212243011;