chr1-155015050-C-T

Variant names:

• chr1-155015050-C-T
• rs11264295
• NM_001256455.2:c.390C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001256455.2(ZBTB7B):​c.390C>T​(p.Ile130Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,613,498 control chromosomes in the GnomAD database, including 184,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18609 hom., cov: 32)
  • Exomes 𝑓: 0.46 (165643 hom.)
• Consequence: ZBTB7B NM_001256455.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.72
• Publications: 25 publications found

Genes affected

ZBTB7B (HGNC:18668): (zinc finger and BTB domain containing 7B) This gene encodes a zinc finger-containing transcription factor that acts as a key regulator of lineage commitment of immature T-cell precursors. It is necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. It also functions as a transcriptional repressor of type I collagen genes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 1-155015050-C-T is Benign according to our data. Variant chr1-155015050-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256455.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB7B	NM_001256455.2	MANE Select	c.390C>T	p.Ile130Ile	synonymous	Exon 2 of 3	NP_001243384.1	O15156-1
	ZBTB7B	NM_001252406.3		c.492C>T	p.Ile164Ile	synonymous	Exon 4 of 5	NP_001239335.1	O15156-2
	ZBTB7B	NM_001377451.1		c.492C>T	p.Ile164Ile	synonymous	Exon 5 of 6	NP_001364380.1	O15156-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB7B	ENST00000535420.6	TSL:5 MANE Select	c.390C>T	p.Ile130Ile	synonymous	Exon 2 of 3	ENSP00000438647.1	O15156-1
	ZBTB7B	ENST00000292176.2	TSL:1	c.390C>T	p.Ile130Ile	synonymous	Exon 1 of 2	ENSP00000292176.2	O15156-1
	ZBTB7B	ENST00000368426.3	TSL:1	c.390C>T	p.Ile130Ile	synonymous	Exon 3 of 4	ENSP00000357411.3	O15156-1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73478 AN: 151816 Hom.: 18617 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.478

GnomAD2 exomes AF: 0.534 AC: 133576 AN: 250252 AF XY: 0.531

Gnomad AFR exome AF: 0.470

Gnomad AMR exome AF: 0.675

Gnomad ASJ exome AF: 0.544

Gnomad EAS exome AF: 0.899

Gnomad FIN exome AF: 0.448

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.507

GnomAD4 exome AF: 0.464 AC: 678056 AN: 1461564 Hom.: 165643 Cov.: 92 AF XY: 0.470 AC XY: 341595 AN XY: 727090

African (AFR) AF: 0.484 AC: 16196 AN: 33480

American (AMR) AF: 0.666 AC: 29797 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 14076 AN: 26136

East Asian (EAS) AF: 0.913 AC: 36244 AN: 39696

South Asian (SAS) AF: 0.647 AC: 55826 AN: 86258

European-Finnish (FIN) AF: 0.454 AC: 24129 AN: 53136

Middle Eastern (MID) AF: 0.568 AC: 3279 AN: 5768

European-Non Finnish (NFE) AF: 0.421 AC: 468472 AN: 1111988

Other (OTH) AF: 0.497 AC: 30037 AN: 60388

GnomAD4 genome AF: 0.484 AC: 73503 AN: 151934 Hom.: 18609 Cov.: 32 AF XY: 0.492 AC XY: 36563 AN XY: 74264

African (AFR) AF: 0.476 AC: 19729 AN: 41416

American (AMR) AF: 0.586 AC: 8959 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1878 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4637 AN: 5156

South Asian (SAS) AF: 0.665 AC: 3202 AN: 4818

European-Finnish (FIN) AF: 0.445 AC: 4703 AN: 10566

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28929 AN: 67912

Other (OTH) AF: 0.475 AC: 1004 AN: 2112

Alfa AF: 0.451 Hom.: 46196

Bravo AF: 0.493

Asia WGS AF: 0.709 AC: 2462 AN: 3478

EpiCase AF: 0.442

EpiControl AF: 0.443

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.4
DANN	Benign	0.93
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs11264295; hg19: chr1-154987526; COSMIC: COSV52694151; COSMIC: COSV52694151;