rs8177262

Variant names:

• chr3-133761808-G-A
• rs8177262
• NM_001063.4:c.1204-2374G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-133761808-G-A
• chr3-133761808-G-C

Variant summary

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

The NM_001063.4(TF):​c.1204-2374G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,940 control chromosomes in the GnomAD database, including 7,877 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 0.31 (7829 hom., cov: 33)
  • Exomes 𝑓: 0.33 (48 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 5 publications found

Genes affected

TF (HGNC:11740): (transferrin) This gene encodes a glycoprotein with an approximate molecular weight of 76.5 kDa. It is thought to have been created as a result of an ancient gene duplication event that led to generation of homologous C and N-terminal domains each of which binds one ion of ferric iron. The function of this protein is to transport iron from the intestine, reticuloendothelial system, and liver parenchymal cells to all proliferating cells in the body. This protein may also have a physiologic role as granulocyte/pollen-binding protein (GPBP) involved in the removal of certain organic matter and allergens from serum. [provided by RefSeq, Sep 2009]

ACSL3P1 (HGNC:56529): (ACSL3 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.1204-2374G>A		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.1072-2374G>A		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.823-2374G>A		intron	N/A	NP_001341633.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.1204-2374G>A		intron	N/A	ENSP00000385834.3
	ACSL3P1	ENST00000474389.1	TSL:6	n.1362G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47400 AN: 151982 Hom.: 7818 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.326 AC: 274 AN: 840 Hom.: 48 Cov.: 0 AF XY: 0.318 AC XY: 149 AN XY: 468

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.450 AC: 9 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AF: 0.278 AC: 5 AN: 18

South Asian (SAS) AF: 0.875 AC: 7 AN: 8

European-Finnish (FIN) AF: 0.308 AC: 180 AN: 584

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.330 AC: 58 AN: 176

Other (OTH) AF: 0.462 AC: 12 AN: 26

GnomAD4 genome AF: 0.312 AC: 47450 AN: 152100 Hom.: 7829 Cov.: 33 AF XY: 0.313 AC XY: 23303 AN XY: 74362

African (AFR) AF: 0.227 AC: 9406 AN: 41498

American (AMR) AF: 0.386 AC: 5903 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2200 AN: 5170

South Asian (SAS) AF: 0.424 AC: 2045 AN: 4822

European-Finnish (FIN) AF: 0.287 AC: 3035 AN: 10576

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22842 AN: 67972

Other (OTH) AF: 0.316 AC: 668 AN: 2114

Alfa AF: 0.298 Hom.: 2036

Bravo AF: 0.315

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.48
DANN	Benign	0.79
PhyloP100		0.36
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: rs8177262; hg19: chr3-133480652; COSMIC: COSV53918871; COSMIC: COSV53918871;