rs752940502

Variant names:

• chr6-56981848-C-T
• rs752940502
• NM_152731.3:c.38C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152731.3(BEND6):​c.38C>T​(p.Thr13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: BEND6 NM_152731.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0860
• Publications: 0 publications found

Genes affected

BEND6 (HGNC:20871): (BEN domain containing 6) Enables transcription corepressor activity. Predicted to be involved in negative regulation of Notch signaling pathway and positive regulation of neuron differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0344944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152731.3. 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
	BEND6	NM_152731.3	MANE Select	c.38C>T	p.Thr13Ile	missense	Exon 2 of 7	NP_689944.2	Q5SZJ8-1
	BEND6	NM_001318539.2		c.38C>T	p.Thr13Ile	missense	Exon 2 of 4	NP_001305468.1	Q5SZJ8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEND6	ENST00000370746.8	TSL:5 MANE Select	c.38C>T	p.Thr13Ile	missense	Exon 2 of 7	ENSP00000359782.3	Q5SZJ8-1
	BEND6	ENST00000370748.7	TSL:1	c.38C>T	p.Thr13Ile	missense	Exon 2 of 4	ENSP00000359784.3	Q5SZJ8-2
	BEND6	ENST00000885664.1		c.38C>T	p.Thr13Ile	missense	Exon 3 of 8	ENSP00000555723.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248266 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460342 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726476

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111256

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.086
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.044
Sift	Benign	0.23	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.092
MutPred		0.23		Loss of phosphorylation at T13 (P = 0.0445)
MVP		0.048
MPC		0.17
ClinPred		0.020	T
GERP RS		-1.6
Varity_R		0.043
gMVP		0.26
Mutation Taster		=98/2	polymorphism

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: rs752940502; hg19: chr6-56846646;