5-39110312-A-T

Variant names:

• chr5-39110312-A-T
• rs77289629
• NM_001465.6:c.2435+44T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001465.6(FYB1):​c.2435+44T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,333,202 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (124 hom.)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.129
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-39110312-A-T is Benign according to our data. Variant chr5-39110312-A-T is described in ClinVar as Benign. ClinVar VariationId is 1256832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0182 (2764/152170) while in subpopulation EAS AF = 0.0513 (266/5186). AF 95% confidence interval is 0.0493. There are 51 homozygotes in GnomAd4. There are 1381 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

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.2435+44T>A		intron	N/A	NP_001456.3
	FYB1	NM_001243093.2		c.2465+44T>A		intron	N/A	NP_001230022.1	O15117-3
	FYB1	NM_001349333.2		c.2435+44T>A		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.2435+44T>A		intron	N/A	ENSP00000425845.3	O15117-2
	FYB1	ENST00000351578.12	TSL:1	c.2297+44T>A		intron	N/A	ENSP00000316460.7	O15117-1
	FYB1	ENST00000515010.5	TSL:1	c.2297+44T>A		intron	N/A	ENSP00000426346.1	O15117-1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2763 AN: 152052 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00656

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.00801

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0108 AC: 2312 AN: 214904 AF XY: 0.00981

Gnomad AFR exome AF: 0.0514

Gnomad AMR exome AF: 0.00343

Gnomad ASJ exome AF: 0.00269

Gnomad EAS exome AF: 0.0476

Gnomad FIN exome AF: 0.00929

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.00930

GnomAD4 exome AF: 0.00481 AC: 5684 AN: 1181032 Hom.: 124 Cov.: 16 AF XY: 0.00496 AC XY: 2960 AN XY: 596512

African (AFR) AF: 0.0520 AC: 1370 AN: 26366

American (AMR) AF: 0.00392 AC: 136 AN: 34710

Ashkenazi Jewish (ASJ) AF: 0.00306 AC: 69 AN: 22550

East Asian (EAS) AF: 0.0482 AC: 1809 AN: 37494

South Asian (SAS) AF: 0.0163 AC: 1090 AN: 66914

European-Finnish (FIN) AF: 0.00837 AC: 428 AN: 51122

Middle Eastern (MID) AF: 0.00391 AC: 18 AN: 4604

European-Non Finnish (NFE) AF: 0.000373 AC: 331 AN: 887048

Other (OTH) AF: 0.00862 AC: 433 AN: 50224

GnomAD4 genome AF: 0.0182 AC: 2764 AN: 152170 Hom.: 51 Cov.: 32 AF XY: 0.0186 AC XY: 1381 AN XY: 74400

African (AFR) AF: 0.0511 AC: 2123 AN: 41550

American (AMR) AF: 0.00656 AC: 100 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.0513 AC: 266 AN: 5186

South Asian (SAS) AF: 0.0190 AC: 92 AN: 4832

European-Finnish (FIN) AF: 0.00801 AC: 85 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 67952

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.00916 Hom.: 5

Bravo AF: 0.0196

Asia WGS AF: 0.0350 AC: 120 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.78
PhyloP100		0.13
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: rs77289629; hg19: chr5-39110414; COSMIC: COSV60949704;