chr19-12792245-C-A

Variant names:

• chr19-12792245-C-A
• rs2229510
• NM_002229.3:c.474C>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_002229.3(JUNB):​c.474C>A​(p.Ser158Ser) 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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3269 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JUNB	NM_002229.3	c.474C>A	p.Ser158Ser	synonymous_variant	Exon 1 of 1	ENST00000302754.6	NP_002220.1
HOOK2	NM_001400043.1	c.-209+79G>T		intron_variant	Intron 1 of 21		NP_001386972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JUNB	ENST00000302754.6	c.474C>A	p.Ser158Ser	synonymous_variant	Exon 1 of 1	6	NM_002229.3	ENSP00000303315.4
HOOK2	ENST00000589765.1	n.42-18020G>T		intron_variant	Intron 3 of 3	5
HOOK2	ENST00000593143.5	n.259+79G>T		intron_variant	Intron 1 of 2	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

GnomAD2 exomes AF: 0.0182 AC: 2132 AN: 116958 AF XY: 0.0181

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 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

African (AFR) AF: 0.00429 AC: 130 AN: 30278

American (AMR) AF: 0.00812 AC: 233 AN: 28678

Ashkenazi Jewish (ASJ) AF: 0.00819 AC: 181 AN: 22094

East Asian (EAS) AF: 0.00 AC: 0 AN: 35826

South Asian (SAS) AF: 0.00416 AC: 312 AN: 75030

European-Finnish (FIN) AF: 0.0311 AC: 1443 AN: 46336

Middle Eastern (MID) AF: 0.00128 AC: 7 AN: 5462

European-Non Finnish (NFE) AF: 0.0341 AC: 36143 AN: 1058876

Other (OTH) AF: 0.0211 AC: 1181 AN: 56012

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

African (AFR) AF: 0.00578 AC: 240 AN: 41542

American (AMR) AF: 0.0116 AC: 177 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4830

European-Finnish (FIN) AF: 0.0319 AC: 339 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0356 AC: 2420 AN: 67956

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.0268 Hom.: 41

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
PhyloP100		-0.099
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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