rs45507496

Variant names:

• chr13-113129397-G-GGGAGCCTGGGTGAAGA
• rs45507496
• NM_000504.4:c.71-42_71-41insAGAGGAGCCTGGGTGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000504.4(F10):​c.71-42_71-41insAGAGGAGCCTGGGTGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,602,334 control chromosomes in the GnomAD database, including 16,619 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1420 hom., cov: 30)
  • Exomes 𝑓: 0.14 (15199 hom.)
• Consequence: F10 NM_000504.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103
• Publications: 2 publications found

Genes affected

F10 (HGNC:3528): (coagulation factor X) This gene encodes the vitamin K-dependent coagulation factor X of the blood coagulation cascade. This factor undergoes multiple processing steps before its preproprotein is converted to a mature two-chain form by the excision of the tripeptide RKR. Two chains of the factor are held together by 1 or more disulfide bonds; the light chain contains 2 EGF-like domains, while the heavy chain contains the catalytic domain which is structurally homologous to those of the other hemostatic serine proteases. The mature factor is activated by the cleavage of the activation peptide by factor IXa (in the intrisic pathway), or by factor VIIa (in the extrinsic pathway). The activated factor then converts prothrombin to thrombin in the presence of factor Va, Ca+2, and phospholipid during blood clotting. Mutations of this gene result in factor X deficiency, a hemorrhagic condition of variable severity. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

F10-AS1 (HGNC:40225): (F10 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-113129397-G-GGGAGCCTGGGTGAAGA is Benign according to our data. Variant chr13-113129397-G-GGGAGCCTGGGTGAAGA is described in ClinVar as Benign. ClinVar VariationId is 1178123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000504.4. 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
	F10	NM_000504.4	MANE Select	c.71-42_71-41insAGAGGAGCCTGGGTGA		intron	N/A	NP_000495.1	Q5JVE7
	F10	NM_001312674.2		c.71-42_71-41insAGAGGAGCCTGGGTGA		intron	N/A	NP_001299603.1
	F10	NM_001312675.2		c.71-42_71-41insAGAGGAGCCTGGGTGA		intron	N/A	NP_001299604.1	Q5JVE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F10	ENST00000375559.8	TSL:1 MANE Select	c.71-55_71-54insGGAGCCTGGGTGAAGA		intron	N/A	ENSP00000364709.3	P00742
	F10	ENST00000375551.7	TSL:1	c.71-55_71-54insGGAGCCTGGGTGAAGA		intron	N/A	ENSP00000364701.3	Q5JVE8
	F10	ENST00000410083.6	TSL:1	n.71-55_71-54insGGAGCCTGGGTGAAGA		intron	N/A	ENSP00000386320.2	F8WBM7

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19755 AN: 151922 Hom.: 1420 Cov.: 30

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.139 AC: 201455 AN: 1450296 Hom.: 15199 AF XY: 0.142 AC XY: 102882 AN XY: 722010

African (AFR) AF: 0.112 AC: 3714 AN: 33232

American (AMR) AF: 0.0898 AC: 4008 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5303 AN: 26038

East Asian (EAS) AF: 0.0187 AC: 741 AN: 39676

South Asian (SAS) AF: 0.219 AC: 18759 AN: 85682

European-Finnish (FIN) AF: 0.114 AC: 6038 AN: 53176

Middle Eastern (MID) AF: 0.196 AC: 844 AN: 4296

European-Non Finnish (NFE) AF: 0.139 AC: 153628 AN: 1103694

Other (OTH) AF: 0.141 AC: 8420 AN: 59868

GnomAD4 genome AF: 0.130 AC: 19761 AN: 152038 Hom.: 1420 Cov.: 30 AF XY: 0.129 AC XY: 9612 AN XY: 74362

African (AFR) AF: 0.114 AC: 4744 AN: 41452

American (AMR) AF: 0.121 AC: 1849 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3466

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5180

South Asian (SAS) AF: 0.205 AC: 985 AN: 4794

European-Finnish (FIN) AF: 0.109 AC: 1155 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9747 AN: 67958

Other (OTH) AF: 0.146 AC: 309 AN: 2110

Alfa AF: 0.128 Hom.: 88

Asia WGS AF: 0.104 AC: 360 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
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs45507496; hg19: chr13-113783711; COSMIC: COSV106064306; COSMIC: COSV106064306;