rs2066865

Variant names:

• chr4-154604124-G-A
• rs2066865
• NM_021870.3:c.*710C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-154604124-G-A
• chr4-154604124-G-C
• chr4-154604124-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021870.3(FGG):​c.*710C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 414,858 control chromosomes in the GnomAD database, including 15,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5650 hom., cov: 32)
  • Exomes 𝑓: 0.26 (10007 hom.)
• Consequence: FGG NM_021870.3 downstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.104
• Publications: 135 publications found

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]

FGG Gene-Disease associations (from GenCC):

• congenital fibrinogen deficiency

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• familial dysfibrinogenemia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• thrombophilia

  Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp
• congenital afibrinogenemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• familial hypofibrinogenemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-154604124-G-A is Benign according to our data. Variant chr4-154604124-G-A is described in ClinVar as Benign. ClinVar VariationId is 369438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGG	NM_021870.3	c.*710C>T		downstream_gene_variant		ENST00000336098.8	NP_068656.2
FGG	NM_000509.6	c.*216C>T		downstream_gene_variant			NP_000500.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGG	ENST00000336098.8	c.*710C>T		downstream_gene_variant		2	NM_021870.3	ENSP00000336829.3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40402 AN: 151920 Hom.: 5640 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.262 AC: 68902 AN: 262820 Hom.: 10007 Cov.: 4 AF XY: 0.261 AC XY: 34854 AN XY: 133778

African (AFR) AF: 0.289 AC: 1952 AN: 6760

American (AMR) AF: 0.211 AC: 1436 AN: 6820

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 1345 AN: 8996

East Asian (EAS) AF: 0.486 AC: 10388 AN: 21360

South Asian (SAS) AF: 0.293 AC: 1915 AN: 6534

European-Finnish (FIN) AF: 0.303 AC: 9484 AN: 31350

Middle Eastern (MID) AF: 0.165 AC: 324 AN: 1960

European-Non Finnish (NFE) AF: 0.235 AC: 38137 AN: 162544

Other (OTH) AF: 0.238 AC: 3921 AN: 16496

GnomAD4 genome AF: 0.266 AC: 40446 AN: 152038 Hom.: 5650 Cov.: 32 AF XY: 0.268 AC XY: 19914 AN XY: 74332

African (AFR) AF: 0.302 AC: 12534 AN: 41454

American (AMR) AF: 0.222 AC: 3391 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3466

East Asian (EAS) AF: 0.446 AC: 2310 AN: 5178

South Asian (SAS) AF: 0.294 AC: 1417 AN: 4818

European-Finnish (FIN) AF: 0.295 AC: 3114 AN: 10558

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16427 AN: 67970

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.245 Hom.: 13790

Bravo AF: 0.263

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31582554, 16144795, 17445871, 19492150, 17403086, 25772935) -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital afibrinogenemia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		0.10
Mutation Taster		=97/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2066865; hg19: chr4-155525276;