rs398123537

Variant names:

• chrX-14857956-TAATAAATA-T
• rs398123537
• NM_001018113.3:c.1105-10_1105-3delTATTTATT

Your query was ambiguous. Multiple possible variants found:

• chrX-14857956-TAATAAATA-T
• chrX-14857956-TAATAAATA-TAATA
• chrX-14857956-TAATAAATA-TAATAAATAAATA
• chrX-14857956-TAATAAATA-TAATAAATAAATAAATA

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001018113.3(FANCB):​c.1105-10_1105-3delTATTTATT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,066,049 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., 6 hem., cov: 22)
  • Exomes 𝑓: 0.000051 (0 hom. 11 hem.)
• Consequence: FANCB NM_001018113.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.429
• 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: ClinGen, G2P, 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
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant X-14857956-TAATAAATA-T is Benign according to our data. Variant chrX-14857956-TAATAAATA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 281376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 6 AR,XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCB	NM_001018113.3	MANE Select	c.1105-10_1105-3delTATTTATT		splice_region intron	N/A	NP_001018123.1	Q8NB91
	FANCB	NM_001410764.1		c.1105-10_1105-3delTATTTATT		splice_region intron	N/A	NP_001397693.1	A0A8Q3WL66
	FANCB	NM_001324162.2		c.1105-10_1105-3delTATTTATT		splice_region intron	N/A	NP_001311091.1	Q8NB91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCB	ENST00000650831.1	MANE Select	c.1105-10_1105-3delTATTTATT		splice_region intron	N/A	ENSP00000498215.1	Q8NB91
	FANCB	ENST00000324138.7	TSL:1	c.1105-10_1105-3delTATTTATT		splice_region intron	N/A	ENSP00000326819.3	Q8NB91
	FANCB	ENST00000452869.2	TSL:1	c.1105-10_1105-3delTATTTATT		splice_region intron	N/A	ENSP00000397849.2	C9J5X9

Frequencies

GnomAD3 genomes AF: 0.000242 AC: 27 AN: 111701 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000783

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000286

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000152 AC: 27 AN: 177339 AF XY: 0.000111

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.0000380

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000877

Gnomad OTH exome AF: 0.000230

GnomAD4 exome AF: 0.0000513 AC: 49 AN: 954301 Hom.: 0 AF XY: 0.0000413 AC XY: 11 AN XY: 266117

African (AFR) AF: 0.00120 AC: 28 AN: 23294

American (AMR) AF: 0.000146 AC: 5 AN: 34359

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18278

East Asian (EAS) AF: 0.00 AC: 0 AN: 29460

South Asian (SAS) AF: 0.0000202 AC: 1 AN: 49558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40163

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3154

European-Non Finnish (NFE) AF: 0.0000126 AC: 9 AN: 714766

Other (OTH) AF: 0.000145 AC: 6 AN: 41269

GnomAD4 genome AF: 0.000242 AC: 27 AN: 111748 Hom.: 0 Cov.: 22 AF XY: 0.000176 AC XY: 6 AN XY: 34012

African (AFR) AF: 0.000782 AC: 24 AN: 30708

American (AMR) AF: 0.000286 AC: 3 AN: 10491

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3583

South Asian (SAS) AF: 0.00 AC: 0 AN: 2742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5985

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53174

Other (OTH) AF: 0.00 AC: 0 AN: 1516

Alfa AF: 0.000110 Hom.: 5

Bravo AF: 0.000544

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Fanconi anemia (2)
-	-	1	FANCB-related disorder (1)
-	-	1	Fanconi anemia complementation group B;C2931228:VACTERL association, X-linked, with or without hydrocephalus (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43
Mutation Taster		=88/12	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs398123537; hg19: chrX-14876078;