rs2066879

chr4-154604563-G-A

Variant summary

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

The NM_021870.3(FGG):c.*271C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,151,626 control chromosomes in the GnomAD database, including 46 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 0.012 (28 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (18 hom.)
• Consequence: FGG NM_021870.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772

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=-0.82).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1833/152136) while in subpopulation AFR AF= 0.0417 (1732/41526). AF 95% confidence interval is 0.0401. There are 28 homozygotes in gnomad4. There are 860 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGG	NM_021870.3	c.*271C>T		3_prime_UTR_variant	9/9	ENST00000336098.8
FGG	NM_000509.6	c.1300-209C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGG	ENST00000336098.8	c.*271C>T		3_prime_UTR_variant	9/9	2	NM_021870.3

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1833 AN: 152018 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.000950 AC: 950 AN: 999490 Hom.: 18 Cov.: 15 AF XY: 0.000871 AC XY: 426 AN XY: 489160

Gnomad4 AFR exome AF: 0.0365

Gnomad4 AMR exome AF: 0.00251

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000150

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000648

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.0120 AC: 1833 AN: 152136 Hom.: 28 Cov.: 33 AF XY: 0.0116 AC XY: 860 AN XY: 74388

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00943 Hom.: 1

Bravo AF: 0.0134

Asia WGS AF: 0.00146 AC: 5 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.5
Dann	Benign	0.60

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: rs2066879; hg19: chr4-155525715;