11-66003187-A-G

Position:

• chr11-66003187-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003860.4(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 NM_003860.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0880

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 1266370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66003187-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANF1	NM_003860.4	c.-16-48A>G		intron_variant		ENST00000312175.7	NP_003851.1
BANF1	NM_001143985.1	c.-16-48A>G		intron_variant			NP_001137457.1
BANF1	XM_017018515.3	c.-16-48A>G		intron_variant			XP_016874004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANF1	ENST00000312175.7	c.-16-48A>G		intron_variant		1	NM_003860.4	ENSP00000310275	P1

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

Gnomad4 AFR exome AF: 0.579

Gnomad4 AMR exome AF: 0.874

Gnomad4 ASJ exome AF: 0.736

Gnomad4 EAS exome AF: 0.841

Gnomad4 SAS exome AF: 0.793

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.805

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

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.754

Alfa AF: 0.809 Hom.: 24793

Bravo AF: 0.750

Asia WGS AF: 0.808 AC: 2805 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.62

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: rs1786172; hg19: chr11-65770658;