rs147260208

Variant names:

• chrX-14865109-T-C
• rs147260208
• NM_001018113.3:c.402A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001018113.3(FANCB):​c.402A>G​(p.Leu134Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,208,183 control chromosomes in the GnomAD database, including 21 homozygotes. There are 382 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (11 hom., 191 hem., cov: 23)
  • Exomes 𝑓: 0.00065 (10 hom. 191 hem.)
• Consequence: FANCB NM_001018113.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.78
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-14865109-T-C is Benign according to our data. Variant chrX-14865109-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 368032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00648 (728/112266) while in subpopulation AFR AF = 0.0227 (703/30993). AF 95% confidence interval is 0.0213. There are 11 homozygotes in GnomAd4. There are 191 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 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.402A>G	p.Leu134Leu	synonymous	Exon 3 of 10	NP_001018123.1	Q8NB91
	FANCB	NM_001410764.1		c.402A>G	p.Leu134Leu	synonymous	Exon 3 of 13	NP_001397693.1	A0A8Q3WL66
	FANCB	NM_001324162.2		c.402A>G	p.Leu134Leu	synonymous	Exon 3 of 10	NP_001311091.1	Q8NB91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCB	ENST00000650831.1	MANE Select	c.402A>G	p.Leu134Leu	synonymous	Exon 3 of 10	ENSP00000498215.1	Q8NB91
	FANCB	ENST00000324138.7	TSL:1	c.402A>G	p.Leu134Leu	synonymous	Exon 2 of 9	ENSP00000326819.3	Q8NB91
	FANCB	ENST00000452869.2	TSL:1	c.402A>G	p.Leu134Leu	synonymous	Exon 3 of 11	ENSP00000397849.2	C9J5X9

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 728 AN: 112217 Hom.: 11 Cov.: 23

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00199

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: 0.0000188

Gnomad OTH AF: 0.00198

GnomAD2 exomes AF: 0.00194 AC: 350 AN: 180534 AF XY: 0.00118

Gnomad AFR exome AF: 0.0237

Gnomad AMR exome AF: 0.00141

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.000649 AC: 711 AN: 1095917 Hom.: 10 Cov.: 30 AF XY: 0.000528 AC XY: 191 AN XY: 361503

African (AFR) AF: 0.0222 AC: 584 AN: 26294

American (AMR) AF: 0.00163 AC: 57 AN: 34869

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19278

East Asian (EAS) AF: 0.00 AC: 0 AN: 30178

South Asian (SAS) AF: 0.0000374 AC: 2 AN: 53547

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40517

Middle Eastern (MID) AF: 0.000485 AC: 2 AN: 4122

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841101

Other (OTH) AF: 0.00139 AC: 64 AN: 46011

GnomAD4 genome AF: 0.00648 AC: 728 AN: 112266 Hom.: 11 Cov.: 23 AF XY: 0.00554 AC XY: 191 AN XY: 34450

African (AFR) AF: 0.0227 AC: 703 AN: 30993

American (AMR) AF: 0.00198 AC: 21 AN: 10584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2663

East Asian (EAS) AF: 0.00 AC: 0 AN: 3591

South Asian (SAS) AF: 0.00 AC: 0 AN: 2718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6111

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53168

Other (OTH) AF: 0.00195 AC: 3 AN: 1535

Alfa AF: 0.00273 Hom.: 9

Bravo AF: 0.00737

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Fanconi anemia complementation group B (3)
-	-	1	Fanconi anemia (1)
-	-	1	History of neurodevelopmental disorder (1)
-	-	1	not specified (1)
-	-	1	VACTERL association, X-linked, with or without hydrocephalus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.54
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	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: rs147260208; hg19: chrX-14883231; COSMIC: COSV104653186;