rs149695930

Variant names:

• chrX-14850630-G-A
• rs149695930
• NM_001018113.3:c.1371C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-14850630-G-A
• chrX-14850630-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001018113.3(FANCB):​c.1371C>T​(p.Val457Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,188,001 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 127 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., 6 hem., cov: 22)
  • Exomes 𝑓: 0.00037 (0 hom. 121 hem.)
• Consequence: FANCB NM_001018113.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.118
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-14850630-G-A is Benign according to our data. Variant chrX-14850630-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 198442.
• BP7: Synonymous conserved (PhyloP=-0.118 with no splicing effect.
• 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.1371C>T	p.Val457Val	synonymous	Exon 7 of 10	NP_001018123.1	Q8NB91
	FANCB	NM_001410764.1		c.1371C>T	p.Val457Val	synonymous	Exon 7 of 13	NP_001397693.1	A0A8Q3WL66
	FANCB	NM_001324162.2		c.1371C>T	p.Val457Val	synonymous	Exon 7 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.1371C>T	p.Val457Val	synonymous	Exon 7 of 10	ENSP00000498215.1	Q8NB91
	FANCB	ENST00000324138.7	TSL:1	c.1371C>T	p.Val457Val	synonymous	Exon 6 of 9	ENSP00000326819.3	Q8NB91
	FANCB	ENST00000452869.2	TSL:1	c.1371C>T	p.Val457Val	synonymous	Exon 7 of 11	ENSP00000397849.2	C9J5X9

Frequencies

GnomAD3 genomes AF: 0.000300 AC: 33 AN: 109875 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000195

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000493

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000394 AC: 71 AN: 180421 AF XY: 0.000322

Gnomad AFR exome AF: 0.0000771

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000189

Gnomad NFE exome AF: 0.000832

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000370 AC: 399 AN: 1078076 Hom.: 0 Cov.: 26 AF XY: 0.000350 AC XY: 121 AN XY: 345950

African (AFR) AF: 0.0000384 AC: 1 AN: 26020

American (AMR) AF: 0.0000286 AC: 1 AN: 35008

Ashkenazi Jewish (ASJ) AF: 0.0000521 AC: 1 AN: 19189

East Asian (EAS) AF: 0.00 AC: 0 AN: 30065

South Asian (SAS) AF: 0.00 AC: 0 AN: 53393

European-Finnish (FIN) AF: 0.000223 AC: 9 AN: 40433

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4067

European-Non Finnish (NFE) AF: 0.000444 AC: 366 AN: 824488

Other (OTH) AF: 0.000462 AC: 21 AN: 45413

GnomAD4 genome AF: 0.000300 AC: 33 AN: 109925 Hom.: 0 Cov.: 22 AF XY: 0.000186 AC XY: 6 AN XY: 32303

African (AFR) AF: 0.000133 AC: 4 AN: 30182

American (AMR) AF: 0.000195 AC: 2 AN: 10269

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3523

South Asian (SAS) AF: 0.00 AC: 0 AN: 2616

European-Finnish (FIN) AF: 0.000179 AC: 1 AN: 5591

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 209

European-Non Finnish (NFE) AF: 0.000493 AC: 26 AN: 52740

Other (OTH) AF: 0.00 AC: 0 AN: 1490

Alfa AF: 0.000321 Hom.: 3

Bravo AF: 0.000314

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	Fanconi anemia (2)
-	1	1	not provided (2)
-	-	1	Fanconi anemia complementation group B (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	-0.84
CADD	Benign	0.84
DANN	Benign	0.55
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs149695930; hg19: chrX-14868752;