8-22621496-C-T

Variant names:

• chr8-22621496-C-T
• rs779546029
• NM_018688.6:c.688G>A

Variant summary

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

The NM_018688.6(BIN3):​c.688G>A​(p.Asp230Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000688 in 1,613,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: BIN3 NM_018688.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.94
• Publications: 2 publications found

Genes affected

BIN3 (HGNC:1054): (bridging integrator 3) The product of this gene is a member of the BAR domain protein family. The encoded protein is comprised solely of a BAR domain which is predicted to form coiled-coil structures and proposed to mediate dimerization, sense and induce membrane curvature, and bind small GTPases. BAR domain proteins have been implicated in endocytosis, intracellular transport, and a diverse set of other processes. [provided by RefSeq, Jul 2008]

CCAR2 (HGNC:23360): (cell cycle and apoptosis regulator 2) Enables RNA polymerase II complex binding activity and enzyme inhibitor activity. Involved in several processes, including regulation of cellular protein metabolic process; regulation of signal transduction; and regulation of transcription, DNA-templated. Located in several cellular components, including mitochondrial matrix; nucleoplasm; and spindle. Part of DBIRD complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018688.6. 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
	BIN3	NM_018688.6	MANE Select	c.688G>A	p.Asp230Asn	missense	Exon 9 of 9	NP_061158.1	Q9NQY0-1
	BIN3	NM_001363046.2		c.544G>A	p.Asp182Asn	missense	Exon 8 of 8	NP_001349975.1	H7BYV6
	CCAR2	NM_021174.6		c.*1814C>T		3_prime_UTR	Exon 21 of 21	NP_066997.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN3	ENST00000276416.11	TSL:1 MANE Select	c.688G>A	p.Asp230Asn	missense	Exon 9 of 9	ENSP00000276416.6	Q9NQY0-1
	BIN3	ENST00000853250.1		c.700G>A	p.Asp234Asn	missense	Exon 9 of 9	ENSP00000523309.1
	BIN3	ENST00000939253.1		c.625G>A	p.Asp209Asn	missense	Exon 9 of 9	ENSP00000609312.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000113 AC: 28 AN: 246782 AF XY: 0.000112

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000136

Gnomad OTH exome AF: 0.000828

GnomAD4 exome AF: 0.0000643 AC: 94 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39 AN XY: 727082

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000268 AC: 12 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0000513 AC: 57 AN: 1111854

Other (OTH) AF: 0.000149 AC: 9 AN: 60372

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74370

African (AFR) AF: 0.000121 AC: 5 AN: 41450

American (AMR) AF: 0.000458 AC: 7 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000161 Hom.: 0

Bravo AF: 0.000200

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000578 AC: 7

EpiCase AF: 0.000218

EpiControl AF: 0.000178

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	0.15
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.9
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.20
Sift	Benign	0.077	T
Sift4G	Benign	0.33	T
Polyphen		1.0	D
Vest4		0.74
MVP		0.55
ClinPred		0.31	T
GERP RS		3.7
Varity_R		0.067
gMVP		0.60
Mutation Taster		=79/21	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: rs779546029; hg19: chr8-22479009; COSMIC: COSV52383041; COSMIC: COSV52383041;