NM_001018113.3:c.1327-10T>C

Variant names:

• chrX-14850684-A-G
• rs2905223
• NM_001018113.3:c.1327-10T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001018113.3(FANCB):​c.1327-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (11742 hom., 16080 hem., cov: 21)
  • Exomes 𝑓: 0.58 (120219 hom. 169168 hem.)
  • Failed GnomAD Quality Control
• Consequence: FANCB NM_001018113.3 intron
• Scores: Splicing: ADA: 0.00002456
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -1.27
• Publications: 11 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-14850684-A-G is Benign according to our data. Variant chrX-14850684-A-G is described in ClinVar as Benign. ClinVar VariationId is 93467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1327-10T>C		intron	N/A	NP_001018123.1	Q8NB91
	FANCB	NM_001410764.1		c.1327-10T>C		intron	N/A	NP_001397693.1	A0A8Q3WL66
	FANCB	NM_001324162.2		c.1327-10T>C		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.1327-10T>C		intron	N/A	ENSP00000498215.1	Q8NB91
	FANCB	ENST00000324138.7	TSL:1	c.1327-10T>C		intron	N/A	ENSP00000326819.3	Q8NB91
	FANCB	ENST00000452869.2	TSL:1	c.1327-10T>C		intron	N/A	ENSP00000397849.2	C9J5X9

Frequencies

GnomAD3 genomes AF: 0.535 AC: 58196 AN: 108757 Hom.: 11746 Cov.: 21

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.534

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.507

GnomAD2 exomes AF: 0.517 AC: 78766 AN: 152467 AF XY: 0.516

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.555

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.611

Gnomad NFE exome AF: 0.610

Gnomad OTH exome AF: 0.545

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.576 AC: 573309 AN: 995768 Hom.: 120219 Cov.: 18 AF XY: 0.574 AC XY: 169168 AN XY: 294908

African (AFR) AF: 0.478 AC: 11466 AN: 24006

American (AMR) AF: 0.447 AC: 14680 AN: 32814

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 10228 AN: 18258

East Asian (EAS) AF: 0.149 AC: 4357 AN: 29209

South Asian (SAS) AF: 0.427 AC: 21290 AN: 49825

European-Finnish (FIN) AF: 0.611 AC: 23802 AN: 38953

Middle Eastern (MID) AF: 0.558 AC: 2061 AN: 3692

European-Non Finnish (NFE) AF: 0.610 AC: 461737 AN: 756560

Other (OTH) AF: 0.558 AC: 23688 AN: 42451

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.535 AC: 58192 AN: 108802 Hom.: 11742 Cov.: 21 AF XY: 0.514 AC XY: 16080 AN XY: 31290

African (AFR) AF: 0.477 AC: 14263 AN: 29915

American (AMR) AF: 0.479 AC: 4892 AN: 10220

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1416 AN: 2603

East Asian (EAS) AF: 0.171 AC: 600 AN: 3512

South Asian (SAS) AF: 0.387 AC: 992 AN: 2563

European-Finnish (FIN) AF: 0.584 AC: 3162 AN: 5414

Middle Eastern (MID) AF: 0.538 AC: 113 AN: 210

European-Non Finnish (NFE) AF: 0.602 AC: 31443 AN: 52228

Other (OTH) AF: 0.498 AC: 734 AN: 1473

Alfa AF: 0.579 Hom.: 9715

Bravo AF: 0.527

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Fanconi anemia complementation group B (4)
-	-	3	not specified (3)
-	-	2	Fanconi anemia (2)
-	-	2	not provided (2)
-	-	1	VACTERL association, X-linked, with or without hydrocephalus (1)
-	-	1	X-linked central congenital hypothyroidism with late-onset testicular enlargement (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs2905223; hg19: chrX-14868806; COSMIC: COSV60762278;