11-66002309-T-G

Position:

• chr11-66002309-T-G

Variant summary

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

The ENST00000445560.6(BANF1):​c.-221T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,190 control chromosomes in the GnomAD database, including 12,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12955 hom., cov: 33)
  • Exomes 𝑓: 0.42 (2 hom.)
• Consequence: BANF1 ENST00000445560.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27

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=-0.76).
• BP6: Variant 11-66002309-T-G is Benign according to our data. Variant chr11-66002309-T-G is described in ClinVar as [Benign]. Clinvar id is 305400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66002309-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANF1	NM_001143985.1	c.-221T>G		5_prime_UTR_variant	1/3		NP_001137457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANF1	ENST00000445560.6	c.-221T>G		5_prime_UTR_variant	1/3	1		ENSP00000416128	P1
BANF1	ENST00000530204.1	c.-448T>G		5_prime_UTR_variant	1/3	5		ENSP00000431785
BANF1	ENST00000524663.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60362 AN: 152046 Hom.: 12947 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.423 AC: 11 AN: 26 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 7 AN XY: 14

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.397 AC: 60387 AN: 152164 Hom.: 12955 Cov.: 33 AF XY: 0.398 AC XY: 29635 AN XY: 74410

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.409

Alfa AF: 0.410 Hom.: 2966

Bravo AF: 0.406

Asia WGS AF: 0.503 AC: 1746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Nestor-Guillermo progeria syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.8
DANN	Benign	0.72

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: rs14157; hg19: chr11-65769780;