6-57017234-C-G

Variant names:

• chr6-57017234-C-G
• rs775307108
• NM_152731.3:c.547C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152731.3(BEND6):​c.547C>G​(p.Arg183Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,409,566 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BEND6 NM_152731.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.81
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.547C>G	p.Arg183Gly	missense	Exon 5 of 7	NP_689944.2	Q5SZJ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEND6	ENST00000370746.8	TSL:5 MANE Select	c.547C>G	p.Arg183Gly	missense	Exon 5 of 7	ENSP00000359782.3	Q5SZJ8-1
	BEND6	ENST00000885664.1		c.547C>G	p.Arg183Gly	missense	Exon 6 of 8	ENSP00000555723.1
	BEND6	ENST00000885665.1		c.547C>G	p.Arg183Gly	missense	Exon 5 of 7	ENSP00000555724.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1409566 Hom.: 0 Cov.: 30 AF XY: 0.00000285 AC XY: 2 AN XY: 701208

African (AFR) AF: 0.00 AC: 0 AN: 29978

American (AMR) AF: 0.00 AC: 0 AN: 38056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24766

East Asian (EAS) AF: 0.00 AC: 0 AN: 34628

South Asian (SAS) AF: 0.00 AC: 0 AN: 79306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1087092

Other (OTH) AF: 0.0000173 AC: 1 AN: 57834

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0051	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.8
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.53
Sift	Benign	0.088	T
Sift4G	Benign	0.089	T
Polyphen		0.92	P
Vest4		0.55
MutPred		0.62		Loss of MoRF binding (P = 0.0144)
MVP		0.29
MPC		0.20
ClinPred		0.76	D
GERP RS		4.9
Varity_R		0.25
gMVP		0.54
Mutation Taster		=67/33	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: rs775307108; hg19: chr6-56882032;