chr20-17735771-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANF2	NM_178477.5	c.233C>G	p.Thr78Ser	missense_variant	Exon 4 of 4	ENST00000246090.6	NP_848572.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANF2	ENST00000246090.6	c.233C>G	p.Thr78Ser	missense_variant	Exon 4 of 4	1	NM_178477.5	ENSP00000246090.5
BANF2	ENST00000377805.7	c.233C>G	p.Thr78Ser	missense_variant	Exon 3 of 3	1		ENSP00000367036.3
BANF2	ENST00000545418.2	c.254C>G	p.Thr85Ser	missense_variant	Exon 3 of 3	3		ENSP00000439128.1
BANF2	ENST00000467330.1	n.437C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

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

GnomAD3 exomes AF: 0.312 AC: 78419 AN: 251242 Hom.: 13054 AF XY: 0.309 AC XY: 41912 AN XY: 135776

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 SAS exome AF: 0.352

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

Gnomad4 AFR exome AF: 0.493

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.305

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

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.312

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 v4.3

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;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.15	T;.;T
MetaRNN	Benign	0.00071	T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.43	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.043
MutPred		0.30		.;Gain of disorder (P = 0.0465);Gain of disorder (P = 0.0465);
MPC		0.20
ClinPred		0.0024	T
GERP RS		3.4
Varity_R		0.058
gMVP		0.095

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

Publications

LitVar

Other links and lift over

dbSNP: rs1053993; hg19: chr20-17716416; COSMIC: COSV55725485;