X-14850676-TAAA-TAA

Variant names:

• chrX-14850676-TA-T
• rs202067682
• NM_001018113.3:c.1327-3delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001410764.1(FANCB):​c.1327-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,048,224 control chromosomes in the GnomAD database, including 294 homozygotes. There are 3,223 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (143 hom., 929 hem., cov: 21)
  • Exomes 𝑓: 0.0098 (151 hom. 2294 hem.)
• Consequence: FANCB NM_001410764.1 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.476
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant X-14850676-TA-T is Benign according to our data. Variant chrX-14850676-TA-T is described in ClinVar as Benign. ClinVar VariationId is 93468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001410764.1. 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.1327-3delT		splice_region intron	N/A	NP_001018123.1
	FANCB	NM_001410764.1		c.1327-3delT		splice_region intron	N/A	NP_001397693.1
	FANCB	NM_001324162.2		c.1327-3delT		splice_region intron	N/A	NP_001311091.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 3757 AN: 105487 Hom.: 143 Cov.: 21

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.00156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00972

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.0176

Gnomad NFE AF: 0.00624

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.0184 AC: 2302 AN: 125253 AF XY: 0.0132

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.0121

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00716

Gnomad FIN exome AF: 0.0194

Gnomad NFE exome AF: 0.00740

Gnomad OTH exome AF: 0.0143

GnomAD4 exome AF: 0.00976 AC: 9204 AN: 942709 Hom.: 151 Cov.: 19 AF XY: 0.00860 AC XY: 2294 AN XY: 266641

African (AFR) AF: 0.114 AC: 2595 AN: 22853

American (AMR) AF: 0.0105 AC: 313 AN: 29747

Ashkenazi Jewish (ASJ) AF: 0.00140 AC: 24 AN: 17082

East Asian (EAS) AF: 0.00152 AC: 39 AN: 25600

South Asian (SAS) AF: 0.00921 AC: 412 AN: 44744

European-Finnish (FIN) AF: 0.0160 AC: 601 AN: 37467

Middle Eastern (MID) AF: 0.0166 AC: 59 AN: 3547

European-Non Finnish (NFE) AF: 0.00637 AC: 4596 AN: 721609

Other (OTH) AF: 0.0141 AC: 565 AN: 40060

GnomAD4 genome AF: 0.0357 AC: 3768 AN: 105515 Hom.: 143 Cov.: 21 AF XY: 0.0313 AC XY: 929 AN XY: 29659

African (AFR) AF: 0.109 AC: 3147 AN: 28862

American (AMR) AF: 0.0170 AC: 165 AN: 9712

Ashkenazi Jewish (ASJ) AF: 0.00156 AC: 4 AN: 2570

East Asian (EAS) AF: 0.00 AC: 0 AN: 3355

South Asian (SAS) AF: 0.00980 AC: 24 AN: 2450

European-Finnish (FIN) AF: 0.0130 AC: 65 AN: 5001

Middle Eastern (MID) AF: 0.0146 AC: 3 AN: 206

European-Non Finnish (NFE) AF: 0.00626 AC: 321 AN: 51278

Other (OTH) AF: 0.0276 AC: 39 AN: 1412

Alfa AF: 0.00721 Hom.: 27

Bravo AF: 0.0388

Asia WGS AF: 0.0180 AC: 44 AN: 2514

ClinVar

ClinVar submissions as Germline

Significance: 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 (1)
-	-	1	Fanconi Anemia, X-Linked (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	VACTERL with hydrocephalus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48
Mutation Taster		=99/1	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: rs202067682; hg19: chrX-14868798; COSMIC: COSV60759099;