11-66003187-A-G

Variant names:

• chr11-66003187-A-G
• rs1786172
• NM_003860.4:c.-16-48A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000312175.7(BANF1):​c.-16-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,602,112 control chromosomes in the GnomAD database, including 538,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44996 hom., cov: 29)
  • Exomes 𝑓: 0.82 (493704 hom.)
• Consequence: BANF1 ENST00000312175.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0880
• Publications: 15 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-66003187-A-G is Benign according to our data. Variant chr11-66003187-A-G is described in ClinVar as Benign. ClinVar VariationId is 1266370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000312175.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANF1	NM_003860.4	MANE Select	c.-16-48A>G		intron	N/A	NP_003851.1
	BANF1	NM_001143985.2		c.-16-48A>G		intron	N/A	NP_001137457.1
	BANF1	NM_001440618.1		c.-16-48A>G		intron	N/A	NP_001427547.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANF1	ENST00000312175.7	TSL:1 MANE Select	c.-16-48A>G		intron	N/A	ENSP00000310275.2
	BANF1	ENST00000445560.6	TSL:1	c.-16-48A>G		intron	N/A	ENSP00000416128.2
	BANF1	ENST00000527348.1	TSL:3	c.-16-48A>G		intron	N/A	ENSP00000432867.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115516 AN: 151748 Hom.: 44972 Cov.: 29

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.824 AC: 1194391 AN: 1450244 Hom.: 493704 Cov.: 31 AF XY: 0.823 AC XY: 593363 AN XY: 721414

African (AFR) AF: 0.579 AC: 19214 AN: 33172

American (AMR) AF: 0.874 AC: 38442 AN: 43996

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 19108 AN: 25974

East Asian (EAS) AF: 0.841 AC: 33285 AN: 39580

South Asian (SAS) AF: 0.793 AC: 67681 AN: 85304

European-Finnish (FIN) AF: 0.888 AC: 47180 AN: 53154

Middle Eastern (MID) AF: 0.737 AC: 3041 AN: 4126

European-Non Finnish (NFE) AF: 0.831 AC: 918257 AN: 1105092

Other (OTH) AF: 0.805 AC: 48183 AN: 59846

GnomAD4 genome AF: 0.761 AC: 115586 AN: 151868 Hom.: 44996 Cov.: 29 AF XY: 0.768 AC XY: 57010 AN XY: 74210

African (AFR) AF: 0.584 AC: 24126 AN: 41338

American (AMR) AF: 0.839 AC: 12824 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2611 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4310 AN: 5132

South Asian (SAS) AF: 0.797 AC: 3830 AN: 4806

European-Finnish (FIN) AF: 0.892 AC: 9436 AN: 10584

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 55999 AN: 67946

Other (OTH) AF: 0.754 AC: 1587 AN: 2106

Alfa AF: 0.808 Hom.: 27486

Bravo AF: 0.750

Asia WGS AF: 0.808 AC: 2805 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.62
PhyloP100		0.088
PromoterAI		0.010	Neutral
Mutation Taster		=100/0	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: rs1786172; hg19: chr11-65770658;