rs2161612

Variant names:

• chr5-39106998-A-G
• rs2161612
• NM_001465.6:c.*445T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001465.6(FYB1):​c.*445T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,110 control chromosomes in the GnomAD database, including 8,142 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8127 hom., cov: 32)
  • Exomes 𝑓: 0.33 (15 hom.)
• Consequence: FYB1 NM_001465.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390
• Publications: 7 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: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001465.6	c.*445T>C		3_prime_UTR_variant	Exon 19 of 19	ENST00000512982.4	NP_001456.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB1	ENST00000512982.4	c.*445T>C		3_prime_UTR_variant	Exon 19 of 19	2	NM_001465.6	ENSP00000425845.3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47017 AN: 151780 Hom.: 8129 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.330 AC: 70 AN: 212 Hom.: 15 Cov.: 0 AF XY: 0.402 AC XY: 45 AN XY: 112

African (AFR) AF: 0.250 AC: 2 AN: 8

American (AMR) AF: 0.167 AC: 1 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.357 AC: 5 AN: 14

South Asian (SAS) AF: 0.500 AC: 4 AN: 8

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.362 AC: 55 AN: 152

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.310 AC: 47014 AN: 151898 Hom.: 8127 Cov.: 32 AF XY: 0.310 AC XY: 23008 AN XY: 74226

African (AFR) AF: 0.172 AC: 7124 AN: 41504

American (AMR) AF: 0.346 AC: 5278 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3464

East Asian (EAS) AF: 0.143 AC: 742 AN: 5180

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4824

European-Finnish (FIN) AF: 0.391 AC: 4123 AN: 10548

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26418 AN: 67816

Other (OTH) AF: 0.283 AC: 595 AN: 2102

Alfa AF: 0.364 Hom.: 6514

Bravo AF: 0.298

Asia WGS AF: 0.181 AC: 624 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.75
PhyloP100		0.39
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: rs2161612; hg19: chr5-39107100;