11-66003259-C-A

Variant names:

• chr11-66003259-C-A
• rs150372514
• NM_003860.4:c.9C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003860.4(BANF1):​c.9C>A​(p.Thr3Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T3T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BANF1 NM_003860.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 0 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: Orphanet, ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003860.4. 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
	BANF1	NM_003860.4	MANE Select	c.9C>A	p.Thr3Thr	synonymous	Exon 2 of 3	NP_003851.1	O75531
	BANF1	NM_001143985.2		c.9C>A	p.Thr3Thr	synonymous	Exon 2 of 3	NP_001137457.1
	BANF1	NM_001440618.1		c.9C>A	p.Thr3Thr	synonymous	Exon 2 of 3	NP_001427547.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANF1	ENST00000312175.7	TSL:1 MANE Select	c.9C>A	p.Thr3Thr	synonymous	Exon 2 of 3	ENSP00000310275.2	O75531
	BANF1	ENST00000445560.6	TSL:1	c.9C>A	p.Thr3Thr	synonymous	Exon 2 of 3	ENSP00000416128.2	O75531
	BANF1	ENST00000527348.1	TSL:3	c.9C>A	p.Thr3Thr	synonymous	Exon 2 of 3	ENSP00000432867.1	O75531

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250848 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461344 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727004

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44706

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: 86232

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.7
DANN	Benign	0.85
PhyloP100		-1.0
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs150372514; hg19: chr11-65770730;