rs190579053

Variant names:

• chrX-14843753-G-A
• rs190579053
• NM_001018113.3:c.2394C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001018113.3(FANCB):​c.2394C>T​(p.Val798Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,209,077 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 71 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 0.000045 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.00021 (0 hom. 70 hem.)
• Consequence: FANCB NM_001018113.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.298
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-14843753-G-A is Benign according to our data. Variant chrX-14843753-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 526472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.298 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 70 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.2394C>T	p.Val798Val	synonymous	Exon 10 of 10	NP_001018123.1	Q8NB91
	FANCB	NM_001410764.1		c.2394C>T	p.Val798Val	synonymous	Exon 10 of 13	NP_001397693.1	A0A8Q3WL66
	FANCB	NM_001324162.2		c.2394C>T	p.Val798Val	synonymous	Exon 10 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.2394C>T	p.Val798Val	synonymous	Exon 10 of 10	ENSP00000498215.1	Q8NB91
	FANCB	ENST00000324138.7	TSL:1	c.2394C>T	p.Val798Val	synonymous	Exon 9 of 9	ENSP00000326819.3	Q8NB91
	FANCB	ENST00000452869.2	TSL:1	c.2394C>T	p.Val798Val	synonymous	Exon 10 of 11	ENSP00000397849.2	C9J5X9

Frequencies

GnomAD3 genomes AF: 0.0000450 AC: 5 AN: 111208 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000492 AC: 9 AN: 183082 AF XY: 0.0000296

Gnomad AFR exome AF: 0.0000760

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: 0.0000980

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000210 AC: 230 AN: 1097818 Hom.: 0 Cov.: 30 AF XY: 0.000193 AC XY: 70 AN XY: 363202

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.0000284 AC: 1 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30198

South Asian (SAS) AF: 0.00 AC: 0 AN: 54136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40469

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.000265 AC: 223 AN: 841817

Other (OTH) AF: 0.000108 AC: 5 AN: 46086

GnomAD4 genome AF: 0.0000449 AC: 5 AN: 111259 Hom.: 0 Cov.: 22 AF XY: 0.0000299 AC XY: 1 AN XY: 33495

African (AFR) AF: 0.0000978 AC: 3 AN: 30683

American (AMR) AF: 0.00 AC: 0 AN: 10406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3522

South Asian (SAS) AF: 0.00 AC: 0 AN: 2661

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5899

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53038

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Fanconi anemia (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.46
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

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: rs190579053; hg19: chrX-14861875; COSMIC: COSV100146578;