chr22-41436557-G-A

Variant names:

• chr22-41436557-G-A
• rs61736465
• NM_016272.4:c.789C>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_016272.4(TOB2):​c.789C>T​(p.Asn263Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,609,368 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (87 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (119 hom.)
• Consequence: TOB2 NM_016272.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43
• Publications: 3 publications found

Genes affected

TOB2 (HGNC:11980): (transducer of ERBB2, 2) TOB2 belongs to the TOB (see TOB1; MIM 605523)/BTG1 (MIM 109580) family of antiproliferative proteins, which are involved in the regulation of cell cycle progression.[supplied by OMIM, Apr 2004]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-41436557-G-A is Benign according to our data. Variant chr22-41436557-G-A is described in ClinVar as Benign. ClinVar VariationId is 784421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016272.4. 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
	TOB2	NM_016272.4	MANE Select	c.789C>T	p.Asn263Asn	synonymous	Exon 2 of 2	NP_057356.1	Q14106-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOB2	ENST00000327492.4	TSL:1 MANE Select	c.789C>T	p.Asn263Asn	synonymous	Exon 2 of 2	ENSP00000331305.3	Q14106-1
	TOB2	ENST00000434408.2	TSL:2	c.789C>T	p.Asn263Asn	synonymous	Exon 2 of 2	ENSP00000388549.2	Q14106-1
	TOB2	ENST00000901391.1		c.789C>T	p.Asn263Asn	synonymous	Exon 2 of 2	ENSP00000571450.1

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2913 AN: 152242 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.0605

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.00652 AC: 1540 AN: 236278 AF XY: 0.00531

Gnomad AFR exome AF: 0.0595

Gnomad AMR exome AF: 0.00556

Gnomad ASJ exome AF: 0.0182

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000593

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.00338 AC: 4928 AN: 1457008 Hom.: 119 Cov.: 30 AF XY: 0.00321 AC XY: 2324 AN XY: 724502

African (AFR) AF: 0.0696 AC: 2327 AN: 33424

American (AMR) AF: 0.00638 AC: 277 AN: 43420

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 434 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.00148 AC: 127 AN: 85744

European-Finnish (FIN) AF: 0.000715 AC: 38 AN: 53112

Middle Eastern (MID) AF: 0.0279 AC: 161 AN: 5768

European-Non Finnish (NFE) AF: 0.000968 AC: 1074 AN: 1109748

Other (OTH) AF: 0.00813 AC: 490 AN: 60240

GnomAD4 genome AF: 0.0192 AC: 2918 AN: 152360 Hom.: 87 Cov.: 32 AF XY: 0.0182 AC XY: 1353 AN XY: 74508

African (AFR) AF: 0.0604 AC: 2511 AN: 41574

American (AMR) AF: 0.0110 AC: 169 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00154 AC: 105 AN: 68042

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0100 Hom.: 23

Bravo AF: 0.0218

Asia WGS AF: 0.00751 AC: 27 AN: 3478

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	-0.85
CADD	Benign	0.86
DANN	Benign	0.51
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	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: rs61736465; hg19: chr22-41832561;