rs1053993

Variant names:

• chr20-17735771-C-G
• rs1053993
• NM_178477.5:c.233C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178477.5(BANF2):​c.233C>G​(p.Thr78Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,612,946 control chromosomes in the GnomAD database, including 74,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9600 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64599 hom.)
• Consequence: BANF2 NM_178477.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705
• Publications: 25 publications found

Genes affected

BANF2 (HGNC:16172): (BANF family member 2) Enables identical protein binding activity. Predicted to be involved in chromosome condensation and chromosome segregation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.073581E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178477.5. 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
	BANF2	NM_178477.5	MANE Select	c.233C>G	p.Thr78Ser	missense	Exon 4 of 4	NP_848572.3	Q9H503-1
	BANF2	NM_001159495.2		c.254C>G	p.Thr85Ser	missense	Exon 3 of 3	NP_001152967.1	Q9H503-2
	BANF2	NM_001014977.4		c.233C>G	p.Thr78Ser	missense	Exon 3 of 3	NP_001014977.2	Q9H503-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANF2	ENST00000246090.6	TSL:1 MANE Select	c.233C>G	p.Thr78Ser	missense	Exon 4 of 4	ENSP00000246090.5	Q9H503-1
	BANF2	ENST00000377805.7	TSL:1	c.233C>G	p.Thr78Ser	missense	Exon 3 of 3	ENSP00000367036.3	Q9H503-1
	BANF2	ENST00000545418.2	TSL:3	c.254C>G	p.Thr85Ser	missense	Exon 3 of 3	ENSP00000439128.1	Q9H503-2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51870 AN: 151808 Hom.: 9596 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.315

GnomAD2 exomes AF: 0.312 AC: 78419 AN: 251242 AF XY: 0.309

Gnomad AFR exome AF: 0.494

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.284

GnomAD4 exome AF: 0.294 AC: 428919 AN: 1461020 Hom.: 64599 Cov.: 34 AF XY: 0.294 AC XY: 213898 AN XY: 726814

African (AFR) AF: 0.493 AC: 16496 AN: 33448

American (AMR) AF: 0.276 AC: 12336 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5994 AN: 26132

East Asian (EAS) AF: 0.438 AC: 17388 AN: 39688

South Asian (SAS) AF: 0.350 AC: 30163 AN: 86210

European-Finnish (FIN) AF: 0.278 AC: 14840 AN: 53368

Middle Eastern (MID) AF: 0.229 AC: 1312 AN: 5736

European-Non Finnish (NFE) AF: 0.281 AC: 311967 AN: 1111358

Other (OTH) AF: 0.305 AC: 18423 AN: 60364

GnomAD4 genome AF: 0.342 AC: 51903 AN: 151926 Hom.: 9600 Cov.: 32 AF XY: 0.339 AC XY: 25210 AN XY: 74288

African (AFR) AF: 0.483 AC: 19972 AN: 41382

American (AMR) AF: 0.267 AC: 4079 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2445 AN: 5158

South Asian (SAS) AF: 0.352 AC: 1686 AN: 4794

European-Finnish (FIN) AF: 0.264 AC: 2792 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19284 AN: 67962

Other (OTH) AF: 0.312 AC: 656 AN: 2104

Alfa AF: 0.289 Hom.: 4995

Bravo AF: 0.348

TwinsUK AF: 0.275 AC: 1019

ALSPAC AF: 0.285 AC: 1098

ESP6500AA AF: 0.491 AC: 2165

ESP6500EA AF: 0.275 AC: 2368

ExAC AF: 0.319 AC: 38761

Asia WGS AF: 0.343 AC: 1191 AN: 3478

EpiCase AF: 0.267

EpiControl AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.00071	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.70
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.050
Sift	Benign	0.34	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.043
MutPred		0.30		Gain of disorder (P = 0.0465)
MPC		0.20
ClinPred		0.0024	T
GERP RS		3.4
Varity_R		0.058
gMVP		0.095
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: rs1053993; hg19: chr20-17716416; COSMIC: COSV55725485;