11-66002122-C-T

Variant names:

• chr11-66002122-C-T
• rs117774800
• NM_001242481.2:c.-329G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001242481.2(EIF1AD):​c.-329G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 152,278 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF1AD NM_001242481.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

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]

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]

BANF1 Gene-Disease associations (from GenCC):

• Nestor-Guillermo progeria syndrome

  Inheritance: AR, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 11-66002122-C-T is Benign according to our data. Variant chr11-66002122-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 305396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242481.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF1AD	NM_001242481.2	MANE Select	c.-329G>A		5_prime_UTR	Exon 1 of 6	NP_001229410.1	Q8N9N8
	EIF1AD	NM_001242482.2		c.-305G>A		5_prime_UTR	Exon 1 of 6	NP_001229411.1	Q8N9N8
	EIF1AD	NM_001242483.2		c.-230G>A		5_prime_UTR	Exon 1 of 6	NP_001229412.1	Q8N9N8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF1AD	ENST00000533544.6	TSL:3 MANE Select	c.-329G>A		5_prime_UTR	Exon 1 of 6	ENSP00000434056.1	Q8N9N8
	EIF1AD	ENST00000312234.6	TSL:1	c.-300G>A		5_prime_UTR	Exon 1 of 6	ENSP00000309175.2	Q8N9N8
	EIF1AD	ENST00000526451.5	TSL:1	c.-175G>A		5_prime_UTR	Exon 1 of 6	ENSP00000436644.1	Q8N9N8

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152160 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 36

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152278 Hom.: 2 Cov.: 32 AF XY: 0.000631 AC XY: 47 AN XY: 74446

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0161 AC: 83 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.000695

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Nestor-Guillermo progeria syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		1.2
PromoterAI		-0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs117774800; hg19: chr11-65769593;