rs1049636

Variant names:

• chr4-154604818-G-A
• rs1049636
• NM_021870.3:c.*16C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-154604818-G-A
• chr4-154604818-G-C

Variant summary

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

The NM_021870.3(FGG):​c.*16C>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 0.689 in 1,612,488 control chromosomes in the GnomAD database, including 385,701 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 0.69 (37081 hom., cov: 31)
  • Exomes 𝑓: 0.69 (348620 hom.)
• Consequence: FGG NM_021870.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 39 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGG	NM_021870.3	c.*16C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000336098.8	NP_068656.2
FGG	NM_000509.6	c.1299+79C>T		intron_variant	Intron 9 of 9		NP_000500.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGG	ENST00000336098.8	c.*16C>T		3_prime_UTR_variant	Exon 9 of 9	2	NM_021870.3	ENSP00000336829.3

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105575 AN: 151944 Hom.: 37045 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.697

GnomAD2 exomes AF: 0.666 AC: 167134 AN: 251056 AF XY: 0.670

Gnomad AFR exome AF: 0.766

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.652

Gnomad EAS exome AF: 0.812

Gnomad FIN exome AF: 0.615

Gnomad NFE exome AF: 0.698

Gnomad OTH exome AF: 0.667

GnomAD4 exome AF: 0.689 AC: 1005986 AN: 1460426 Hom.: 348620 Cov.: 47 AF XY: 0.688 AC XY: 500192 AN XY: 726534

African (AFR) AF: 0.769 AC: 25709 AN: 33440

American (AMR) AF: 0.501 AC: 22390 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 17043 AN: 26116

East Asian (EAS) AF: 0.810 AC: 32164 AN: 39694

South Asian (SAS) AF: 0.642 AC: 55301 AN: 86186

European-Finnish (FIN) AF: 0.615 AC: 32814 AN: 53338

Middle Eastern (MID) AF: 0.726 AC: 3984 AN: 5488

European-Non Finnish (NFE) AF: 0.698 AC: 775251 AN: 1111170

Other (OTH) AF: 0.685 AC: 41330 AN: 60320

GnomAD4 genome AF: 0.695 AC: 105657 AN: 152062 Hom.: 37081 Cov.: 31 AF XY: 0.687 AC XY: 51046 AN XY: 74318

African (AFR) AF: 0.762 AC: 31619 AN: 41490

American (AMR) AF: 0.570 AC: 8711 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2194 AN: 3464

East Asian (EAS) AF: 0.803 AC: 4144 AN: 5162

South Asian (SAS) AF: 0.624 AC: 3011 AN: 4824

European-Finnish (FIN) AF: 0.611 AC: 6441 AN: 10538

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47264 AN: 67988

Other (OTH) AF: 0.691 AC: 1456 AN: 2108

Alfa AF: 0.699 Hom.: 137939

Bravo AF: 0.699

Asia WGS AF: 0.681 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		-0.22
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: rs1049636; hg19: chr4-155525970; COSMIC: COSV60194817; COSMIC: COSV60194817;