5-39119142-A-G

Variant names:

• chr5-39119142-A-G
• rs16868122
• NM_001465.6:c.2239-106T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001465.6(FYB1):​c.2239-106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 540,784 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (387 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (100 hom.)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.593
• Publications: 1 publications found

Genes affected

FYB1 (HGNC:4036): (FYN binding protein 1) The protein encoded by this gene is an adapter for the FYN protein and LCP2 signaling cascades in T-cells. The encoded protein is involved in platelet activation and controls the expression of interleukin-2. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

FYB1 Gene-Disease associations (from GenCC):

• thrombocytopenia 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-39119142-A-G is Benign according to our data. Variant chr5-39119142-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239268.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001465.6. 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
	FYB1	NM_001465.6	MANE Select	c.2239-106T>C		intron	N/A	NP_001456.3
	FYB1	NM_001243093.2		c.2269-106T>C		intron	N/A	NP_001230022.1	O15117-3
	FYB1	NM_001349333.2		c.2239-106T>C		intron	N/A	NP_001336262.1	O15117-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	ENST00000512982.4	TSL:2 MANE Select	c.2239-106T>C		intron	N/A	ENSP00000425845.3	O15117-2
	FYB1	ENST00000351578.12	TSL:1	c.2101-106T>C		intron	N/A	ENSP00000316460.7	O15117-1
	FYB1	ENST00000515010.5	TSL:1	c.2101-106T>C		intron	N/A	ENSP00000426346.1	O15117-1

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5791 AN: 152112 Hom.: 385 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.00445 AC: 1730 AN: 388554 Hom.: 100 AF XY: 0.00391 AC XY: 770 AN XY: 197058

African (AFR) AF: 0.134 AC: 1271 AN: 9498

American (AMR) AF: 0.0108 AC: 101 AN: 9372

Ashkenazi Jewish (ASJ) AF: 0.0000928 AC: 1 AN: 10778

East Asian (EAS) AF: 0.00 AC: 0 AN: 24806

South Asian (SAS) AF: 0.000299 AC: 4 AN: 13380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29052

Middle Eastern (MID) AF: 0.00942 AC: 15 AN: 1592

European-Non Finnish (NFE) AF: 0.000339 AC: 91 AN: 268784

Other (OTH) AF: 0.0116 AC: 247 AN: 21292

GnomAD4 genome AF: 0.0382 AC: 5809 AN: 152230 Hom.: 387 Cov.: 33 AF XY: 0.0370 AC XY: 2757 AN XY: 74420

African (AFR) AF: 0.132 AC: 5493 AN: 41548

American (AMR) AF: 0.0132 AC: 202 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 67972

Other (OTH) AF: 0.0321 AC: 68 AN: 2116

Alfa AF: 0.0230 Hom.: 69

Bravo AF: 0.0437

Asia WGS AF: 0.0110 AC: 38 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.59
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: rs16868122; hg19: chr5-39119244;