rs387906871

Variant names:

• chr11-66003284-G-A
• rs387906871
• NM_003860.4:c.34G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_003860.4(BANF1):​c.34G>A​(p.Ala12Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BANF1 NM_003860.4 missense
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: 7.25
• Publications: 39 publications found

Genes affected

BANF1 (HGNC:17397): (BAF nuclear assembly factor 1) The protein encoded by this gene was first identified by its ability to protect retroviruses from intramolecular integration and therefore promote intermolecular integration into the host cell genome. The protein forms a homodimer which localizes to both the nucleus and cytoplasm and is specifically associated with chromosomes during mitosis. This protein binds to double stranded DNA in a non-specific manner and also binds to LEM-domain containing proteins of the nuclear envelope. This protein is thought to facilitate nuclear reassembly by binding with both DNA and inner nuclear membrane proteins and thereby recruit chromatin to the nuclear periphery. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Jan 2009]

BANF1 Gene-Disease associations (from GenCC):

• Nestor-Guillermo progeria syndrome

  Inheritance: AR, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.4299 (below the threshold of 3.09). Trascript score misZ: 2.2879 (below the threshold of 3.09). GenCC associations: The gene is linked to Nestor-Guillermo progeria syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANF1	NM_003860.4	c.34G>A	p.Ala12Thr	missense_variant	Exon 2 of 3	ENST00000312175.7	NP_003851.1
BANF1	NM_001143985.2	c.34G>A	p.Ala12Thr	missense_variant	Exon 2 of 3		NP_001137457.1
BANF1	NM_001440618.1	c.34G>A	p.Ala12Thr	missense_variant	Exon 2 of 3		NP_001427547.1
BANF1	NM_001440619.1	c.34G>A	p.Ala12Thr	missense_variant	Exon 2 of 3		NP_001427548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANF1	ENST00000312175.7	c.34G>A	p.Ala12Thr	missense_variant	Exon 2 of 3	1	NM_003860.4	ENSP00000310275.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461602 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 30

ClinVar

Significance: no classifications from unflagged records

Submissions summary: Pathogenic:1

Revision: no classifications from unflagged records

Submissions by phenotype

Nestor-Guillermo progeria syndrome Pathogenic:1

May 13, 2011

OMIM

Significance: Pathogenic

Review Status: flagged submission

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;D;.;D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-0.62	T
PhyloP100		7.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.040	D;D;D;D;D
Sift4G	Benign	0.070	T;T;D;T;T
Polyphen		0.67	P;P;.;P;P
Vest4		0.76
MutPred		0.39		Gain of glycosylation at A12 (P = 0.0351);Gain of glycosylation at A12 (P = 0.0351);Gain of glycosylation at A12 (P = 0.0351);Gain of glycosylation at A12 (P = 0.0351);Gain of glycosylation at A12 (P = 0.0351);
MVP		0.93
MPC		1.0
ClinPred		1.0	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.48
Mutation Taster		=2/98	disease causing (ClinVar)

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: rs387906871; hg19: chr11-65770755;