11-66003900-C-A

Variant names:

• chr11-66003900-C-A
• rs144367403
• NM_003860.4:c.*128C>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_003860.4(BANF1):​c.*128C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,381,896 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (20 hom., cov: 31)
  • Exomes 𝑓: 0.00081 (12 hom.)
• Consequence: BANF1 NM_003860.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.696
• Publications: 2 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]

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 11-66003900-C-A is Benign according to our data. Variant chr11-66003900-C-A is described in ClinVar as Benign. ClinVar VariationId is 305409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00842 (1281/152222) while in subpopulation AFR AF = 0.0284 (1177/41506). AF 95% confidence interval is 0.027. There are 20 homozygotes in GnomAd4. There are 615 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003860.4. 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
	BANF1	NM_003860.4	MANE Select	c.*128C>A		3_prime_UTR	Exon 3 of 3	NP_003851.1	O75531
	BANF1	NM_001143985.2		c.*128C>A		3_prime_UTR	Exon 3 of 3	NP_001137457.1
	BANF1	NM_001440618.1		c.*128C>A		3_prime_UTR	Exon 3 of 3	NP_001427547.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANF1	ENST00000312175.7	TSL:1 MANE Select	c.*128C>A		3_prime_UTR	Exon 3 of 3	ENSP00000310275.2	O75531
	BANF1	ENST00000445560.6	TSL:1	c.*128C>A		3_prime_UTR	Exon 3 of 3	ENSP00000416128.2	O75531
	BANF1	ENST00000533166.5	TSL:2	c.*128C>A		3_prime_UTR	Exon 3 of 3	ENSP00000433760.1	O75531

Frequencies

GnomAD3 genomes AF: 0.00837 AC: 1273 AN: 152104 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.000812 AC: 998 AN: 1229674 Hom.: 12 Cov.: 17 AF XY: 0.000708 AC XY: 435 AN XY: 614402

African (AFR) AF: 0.0286 AC: 800 AN: 27962

American (AMR) AF: 0.00159 AC: 57 AN: 35820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23944

East Asian (EAS) AF: 0.00 AC: 0 AN: 35500

South Asian (SAS) AF: 0.0000520 AC: 4 AN: 76970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40604

Middle Eastern (MID) AF: 0.00132 AC: 5 AN: 3780

European-Non Finnish (NFE) AF: 0.0000611 AC: 57 AN: 932846

Other (OTH) AF: 0.00144 AC: 75 AN: 52248

GnomAD4 genome AF: 0.00842 AC: 1281 AN: 152222 Hom.: 20 Cov.: 31 AF XY: 0.00826 AC XY: 615 AN XY: 74418

African (AFR) AF: 0.0284 AC: 1177 AN: 41506

American (AMR) AF: 0.00503 AC: 77 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68012

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00789 Hom.: 1

Bravo AF: 0.0100

ClinVar

ClinVar submissions

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	-0.43
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism

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: rs144367403; hg19: chr11-65771371;