11-66002309-T-G

Variant names:

• chr11-66002309-T-G
• rs14157
• ENST00000445560.6:c.-221T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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]

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

Our verdict: Benign. The variant received -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 VariationId is 305400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445560.6. 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
	EIF1AD	NM_001242481.2	MANE Select	c.-516A>C		upstream_gene	N/A	NP_001229410.1
	BANF1	NM_003860.4	MANE Select	c.-278T>G		upstream_gene	N/A	NP_003851.1
	EIF1AD	NM_001242482.2		c.-492A>C		upstream_gene	N/A	NP_001229411.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANF1	ENST00000445560.6	TSL:1	c.-221T>G		5_prime_UTR	Exon 1 of 3	ENSP00000416128.2
	BANF1	ENST00000530204.1	TSL:5	c.-448T>G		5_prime_UTR	Exon 1 of 3	ENSP00000431785.1
	EIF1AD	ENST00000533544.6	TSL:3 MANE Select	c.-516A>C		upstream_gene	N/A	ENSP00000434056.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.125 AC: 1 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.563 AC: 9 AN: 16

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.231 AC: 9579 AN: 41524

American (AMR) AF: 0.549 AC: 8393 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1660 AN: 3470

East Asian (EAS) AF: 0.523 AC: 2703 AN: 5164

South Asian (SAS) AF: 0.454 AC: 2188 AN: 4824

European-Finnish (FIN) AF: 0.378 AC: 3998 AN: 10576

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30424 AN: 68000

Other (OTH) AF: 0.409 AC: 864 AN: 2112

Alfa AF: 0.406 Hom.: 2990

Bravo AF: 0.406

Asia WGS AF: 0.503 AC: 1746 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Nestor-Guillermo progeria syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.8
DANN	Benign	0.72
PhyloP100		-1.3
PromoterAI		-0.051	Neutral
Mutation Taster		=300/0	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: rs14157; hg19: chr11-65769780;