6-149244850-T-C

Position:

• chr6-149244850-T-C

Variant summary

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

The ENST00000635954.1(ENSG00000228408):​n.1489T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 151,532 control chromosomes in the GnomAD database, including 49,063 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 0.80 (49037 hom., cov: 27)
  • Exomes 𝑓: 0.80 (26 hom.)
• Consequence: ENST00000635954.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

Genes affected

(HGNC:):

TAB2-AS1 (HGNC:53508): (TAB2 antisense RNA 1)

TAB2 (HGNC:17075): (TGF-beta activated kinase 1 (MAP3K7) binding protein 2) The protein encoded by this gene is an activator of MAP3K7/TAK1, which is required for for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, and it thus serves as an adaptor that links MAP3K7 and TRAF6. This protein, along with TAB1 and MAP3K7, also participates in the signal transduction induced by TNFSF11/RANKl through the activation of the receptor activator of NF-kappaB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Studies of the related mouse protein indicate that it functions to protect against liver damage caused by chemical stressors. Mutations in this gene cause congenital heart defects, multiple types, 2 (CHTD2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAB2-AS1	NR_149096.1	n.169-849A>G		intron_variant, non_coding_transcript_variant
TAB2	NM_001292035.3	c.6+26074T>C		intron_variant			NP_001278964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000635954.1	n.1489T>C		non_coding_transcript_exon_variant	4/4	5
TAB2-AS1	ENST00000424421.2	n.169-849A>G		intron_variant, non_coding_transcript_variant		5
TAB2	ENST00000606202.1	c.-121+26074T>C		intron_variant		4		ENSP00000476139

Frequencies

GnomAD3 genomes AF: 0.804 AC: 121596 AN: 151332 Hom.: 48993 Cov.: 27

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.810

GnomAD4 exome AF: 0.805 AC: 66 AN: 82 Hom.: 26 Cov.: 0 AF XY: 0.796 AC XY: 43 AN XY: 54

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.803

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.804 AC: 121698 AN: 151450 Hom.: 49037 Cov.: 27 AF XY: 0.800 AC XY: 59191 AN XY: 73966

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.808

Alfa AF: 0.789 Hom.: 5924

Bravo AF: 0.823

Asia WGS AF: 0.802 AC: 2791 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.77
DANN	Benign	0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7747474; hg19: chr6-149565986; COSMIC: COSV70064225;