11-66002338-G-C

Variant names:

• chr11-66002338-G-C
• rs1786171
• ENST00000445560:c.-192G>C

Variant summary

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

The NM_001143985.1(BANF1):​c.-192G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,270 control chromosomes in the GnomAD database, including 39,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39858 hom., cov: 34)
  • Exomes 𝑓: 0.80 (17 hom.)
• Consequence: BANF1 NM_001143985.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630

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]

EIF1AD (HGNC:28147): (eukaryotic translation initiation factor 1A domain containing) Predicted to enable translation initiation factor activity. Predicted to be involved in translational initiation. Located in intermediate filament cytoskeleton and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-66002338-G-C is Benign according to our data. Variant chr11-66002338-G-C is described in ClinVar as [Benign]. Clinvar id is 305401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66002338-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF1AD	NM_001242481.2	c.-545C>G		upstream_gene_variant		ENST00000533544.6	NP_001229410.1
BANF1	NM_003860.4	c.-249G>C		upstream_gene_variant		ENST00000312175.7	NP_003851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF1AD	ENST00000533544.6	c.-545C>G		upstream_gene_variant		3	NM_001242481.2	ENSP00000434056.1
BANF1	ENST00000312175.7	c.-249G>C		upstream_gene_variant		1	NM_003860.4	ENSP00000310275.2

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107793 AN: 152106 Hom.: 39849 Cov.: 34

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.804 AC: 37 AN: 46 Hom.: 17 Cov.: 0 AF XY: 0.853 AC XY: 29 AN XY: 34

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.735

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.708 AC: 107836 AN: 152224 Hom.: 39858 Cov.: 34 AF XY: 0.716 AC XY: 53279 AN XY: 74438

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.871

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.707

Alfa AF: 0.762 Hom.: 5642

Bravo AF: 0.692

Asia WGS AF: 0.743 AC: 2582 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nestor-Guillermo progeria syndrome Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.79
CADD	Benign	4.8
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1786171; hg19: chr11-65769809;