rs2066860

Positions:

• chr4-154608322-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021870.3(FGG):​c.851+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 810,540 control chromosomes in the GnomAD database, including 379 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 0.022 (50 hom., cov: 32)
  • Exomes 𝑓: 0.028 (329 hom.)
• Consequence: FGG NM_021870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

Genes affected

FGG (HGNC:3694): (fibrinogen gamma chain) The protein encoded by this gene is the gamma component of fibrinogen, a blood-borne glycoprotein comprised of three pairs of nonidentical polypeptide chains. Following vascular injury, fibrinogen is cleaved by thrombin to form fibrin which is the most abundant component of blood clots. In addition, various cleavage products of fibrinogen and fibrin regulate cell adhesion and spreading, display vasoconstrictor and chemotactic activities, and are mitogens for several cell types. Mutations in this gene lead to several disorders, including dysfibrinogenemia, hypofibrinogenemia and thrombophilia. Alternative splicing results in transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0223 (3393/152232) while in subpopulation NFE AF= 0.0362 (2459/68008). AF 95% confidence interval is 0.035. There are 50 homozygotes in gnomad4. There are 1565 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGG	NM_021870.3	c.851+144G>A		intron_variant		ENST00000336098.8
FGG	NM_000509.6	c.851+144G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGG	ENST00000336098.8	c.851+144G>A		intron_variant		2	NM_021870.3

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3395 AN: 152114 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.00623

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00227

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0277 AC: 18246 AN: 658308 Hom.: 329 AF XY: 0.0268 AC XY: 9293 AN XY: 346610

Gnomad4 AFR exome AF: 0.00570

Gnomad4 AMR exome AF: 0.0134

Gnomad4 ASJ exome AF: 0.0250

Gnomad4 EAS exome AF: 0.0000926

Gnomad4 SAS exome AF: 0.00334

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.0361

Gnomad4 OTH exome AF: 0.0238

GnomAD4 genome AF: 0.0223 AC: 3393 AN: 152232 Hom.: 50 Cov.: 32 AF XY: 0.0210 AC XY: 1565 AN XY: 74430

Gnomad4 AFR AF: 0.00621

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0165

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0327 Hom.: 27

Bravo AF: 0.0225

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2066860; hg19: chr4-155529474;