X-14850676-TAAA-T

Variant names:

• chrX-14850676-TAAA-T
• rs202067682
• NM_001018113.3:c.1327-5_1327-3delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001018113.3(FANCB):​c.1327-5_1327-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000105 in 952,414 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
• Consequence: FANCB NM_001018113.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 2 publications found

Genes affected

FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

FANCB Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group B

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• VACTERL association, X-linked, with or without hydrocephalus

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• VACTERL with hydrocephalus

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018113.3. 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
	FANCB	NM_001018113.3	MANE Select	c.1327-5_1327-3delTTT		splice_region intron	N/A	NP_001018123.1
	FANCB	NM_001410764.1		c.1327-5_1327-3delTTT		splice_region intron	N/A	NP_001397693.1
	FANCB	NM_001324162.2		c.1327-5_1327-3delTTT		splice_region intron	N/A	NP_001311091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCB	ENST00000650831.1	MANE Select	c.1327-5_1327-3delTTT		splice_region intron	N/A	ENSP00000498215.1
	FANCB	ENST00000324138.7	TSL:1	c.1327-5_1327-3delTTT		splice_region intron	N/A	ENSP00000326819.3
	FANCB	ENST00000452869.2	TSL:1	c.1327-5_1327-3delTTT		splice_region intron	N/A	ENSP00000397849.2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000798 AC: 1 AN: 125253 AF XY: 0.00

Gnomad AFR exome AF: 0.000104

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000105 AC: 1 AN: 952414 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 272200

African (AFR) AF: 0.0000434 AC: 1 AN: 23063

American (AMR) AF: 0.00 AC: 0 AN: 30354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17284

East Asian (EAS) AF: 0.00 AC: 0 AN: 26277

South Asian (SAS) AF: 0.00 AC: 0 AN: 45762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 727816

Other (OTH) AF: 0.00 AC: 0 AN: 40458

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 27

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs202067682; hg19: chrX-14868798;