chr11-66003074-G-A

Position:

• chr11-66003074-G-A

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.-16-161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 738,478 control chromosomes in the GnomAD database, including 40,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7016 hom., cov: 30)
  • Exomes 𝑓: 0.33 (33763 hom.)
• Consequence: BANF1 NM_003860.4 intron
• Scores: Splicing: ADA: 0.0003237
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.13

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=-0.79).
• BP6: Variant 11-66003074-G-A is Benign according to our data. Variant chr11-66003074-G-A is described in ClinVar as [Benign]. Clinvar id is 1296891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANF1	NM_003860.4	c.-16-161G>A		intron_variant		ENST00000312175.7	NP_003851.1
BANF1	NM_001143985.1	c.-16-161G>A		intron_variant			NP_001137457.1
BANF1	XM_017018515.3	c.-16-161G>A		intron_variant			XP_016874004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANF1	ENST00000312175.7	c.-16-161G>A		intron_variant		1	NM_003860.4	ENSP00000310275	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43611 AN: 151868 Hom.: 7015 Cov.: 30

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.327 AC: 191896 AN: 586492 Hom.: 33763 Cov.: 7 AF XY: 0.329 AC XY: 102416 AN XY: 310950

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.287 AC: 43617 AN: 151986 Hom.: 7016 Cov.: 30 AF XY: 0.293 AC XY: 21781 AN XY: 74266

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.273

Alfa AF: 0.237 Hom.: 672

Bravo AF: 0.258

Asia WGS AF: 0.236 AC: 820 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.3
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00032
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.52		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.52		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2276132; hg19: chr11-65770545;