6-149244850-T-C

Variant names:

• chr6-149244850-T-C
• rs7747474
• ENST00000635954.1:n.1489T>C

Variant summary

Our verdict is Benign. The variant received -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: ENSG00000228408 ENST00000635954.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 0 publications found

Genes affected

ENSG00000228408 (HGNC:):

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAB2	NM_001292035.3	c.6+26074T>C		intron_variant	Intron 2 of 6		NP_001278964.1
TAB2-AS1	NR_149096.1	n.169-849A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000228408	ENST00000635954.1	n.1489T>C		non_coding_transcript_exon_variant	Exon 4 of 4	5
TAB2	ENST00000606202.1	c.-121+26074T>C		intron_variant	Intron 1 of 1	4		ENSP00000476139.1
TAB2-AS1	ENST00000424421.3	n.175-849A>G		intron_variant	Intron 1 of 2	5

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

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.803 AC: 53 AN: 66

Other (OTH) AF: 0.875 AC: 7 AN: 8

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

African (AFR) AF: 0.849 AC: 34974 AN: 41208

American (AMR) AF: 0.859 AC: 13081 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2629 AN: 3470

East Asian (EAS) AF: 0.954 AC: 4909 AN: 5148

South Asian (SAS) AF: 0.718 AC: 3445 AN: 4800

European-Finnish (FIN) AF: 0.714 AC: 7440 AN: 10418

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52414 AN: 67858

Other (OTH) AF: 0.808 AC: 1704 AN: 2108

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
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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