rs2229510

chr19-12792245-C-Achr19-12792245-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_002229.3(JUNB):c.474C>A(p.Ser158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,510,778 control chromosomes in the GnomAD database, including 731 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 0.021 (46 hom., cov: 32)
  • Exomes 𝑓: 0.029 (685 hom.)
• Consequence: JUNB NM_002229.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

Genes affected

JUNB (HGNC:6205): (JunB proto-oncogene, AP-1 transcription factor subunit) Enables sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of transcription factor AP-1 complex. Biomarker of Hodgkin's lymphoma and anaplastic large cell lymphoma. [provided by Alliance of Genome Resources, Apr 2022]

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=-0.099 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0215 (3269/152186) while in subpopulation NFE AF= 0.0356 (2420/67956). AF 95% confidence interval is 0.0344. There are 46 homozygotes in gnomad4. There are 1548 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3272 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JUNB	NM_002229.3	c.474C>A	p.Ser158=	synonymous_variant	1/1	ENST00000302754.6
HOOK2	NM_001400043.1	c.-209+79G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JUNB	ENST00000302754.6	c.474C>A	p.Ser158=	synonymous_variant	1/1		NM_002229.3	P1
HOOK2	ENST00000589765.1	n.42-18020G>T		intron_variant, non_coding_transcript_variant		5
HOOK2	ENST00000593143.5	n.259+79G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3272 AN: 152068 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00579

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0319

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0186

GnomAD3 exomes AF: 0.0182 AC: 2132 AN: 116958 Hom.: 31 AF XY: 0.0181 AC XY: 1146 AN XY: 63436

Gnomad AFR exome AF: 0.00532

Gnomad AMR exome AF: 0.00851

Gnomad ASJ exome AF: 0.00840

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00377

Gnomad FIN exome AF: 0.0329

Gnomad NFE exome AF: 0.0310

Gnomad OTH exome AF: 0.0189

GnomAD4 exome AF: 0.0292 AC: 39630 AN: 1358592 Hom.: 685 Cov.: 31 AF XY: 0.0286 AC XY: 19068 AN XY: 666530

Gnomad4 AFR exome AF: 0.00429

Gnomad4 AMR exome AF: 0.00812

Gnomad4 ASJ exome AF: 0.00819

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00416

Gnomad4 FIN exome AF: 0.0311

Gnomad4 NFE exome AF: 0.0341

Gnomad4 OTH exome AF: 0.0211

GnomAD4 genome AF: 0.0215 AC: 3269 AN: 152186 Hom.: 46 Cov.: 32 AF XY: 0.0208 AC XY: 1548 AN XY: 74426

Gnomad4 AFR AF: 0.00578

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0319

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0237 Hom.: 22

Bravo AF: 0.0187

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	7.2
Dann	Benign	0.91
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

Publications

LitVar

Other links and lift over

dbSNP: rs2229510; hg19: chr19-12903059; COSMIC: COSV100040141; COSMIC: COSV100040141;