rs2066861

Variant names:

• chr4-154606284-C-T
• rs2066861
• NM_021870.3:c.1129+421G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-154606284-C-T
• chr4-154606284-C-A
• chr4-154606284-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021870.3(FGG):​c.1129+421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,050 control chromosomes in the GnomAD database, including 5,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5495 hom., cov: 32)
• Consequence: FGG NM_021870.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24
• Publications: 11 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: Orphanet, Labcorp Genetics (formerly Invitae)
• thrombophilia

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287770 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-154606284-C-T is Benign according to our data. Variant chr4-154606284-C-T is described in ClinVar as Benign. ClinVar VariationId is 1234766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021870.3. 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
	FGG	NM_021870.3	MANE Select	c.1129+421G>A		intron	N/A	NP_068656.2	P02679-1
	FGG	NM_000509.6		c.1129+421G>A		intron	N/A	NP_000500.2	P02679-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGG	ENST00000336098.8	TSL:2 MANE Select	c.1129+421G>A		intron	N/A	ENSP00000336829.3	P02679-1
	FGG	ENST00000404648.7	TSL:1	c.1129+421G>A		intron	N/A	ENSP00000384860.3	P02679-2
	FGG	ENST00000407946.5	TSL:5	c.1153+421G>A		intron	N/A	ENSP00000384552.1	C9JC84

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39903 AN: 151932 Hom.: 5488 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.226

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 39941 AN: 152050 Hom.: 5495 Cov.: 32 AF XY: 0.265 AC XY: 19672 AN XY: 74308

African (AFR) AF: 0.292 AC: 12093 AN: 41482

American (AMR) AF: 0.220 AC: 3361 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2276 AN: 5138

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

European-Finnish (FIN) AF: 0.296 AC: 3133 AN: 10586

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

European-Non Finnish (NFE) AF: 0.242 AC: 16415 AN: 67962

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.260 Hom.: 1491

Bravo AF: 0.260

Asia WGS AF: 0.318 AC: 1102 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.37
PhyloP100		-1.2
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: rs2066861; hg19: chr4-155527436;