NM_001063.4:c.635+268G>A

Variant names:

• chr3-133755763-G-A
• rs3811657
• NM_001063.4:c.635+268G>A

Variant summary

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

The NM_001063.4(TF):​c.635+268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 536,678 control chromosomes in the GnomAD database, including 6,339 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 0.13 (1442 hom., cov: 31)
  • Exomes 𝑓: 0.15 (4897 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 2 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]

TF Gene-Disease associations (from GenCC):

• atransferrinemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

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 = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.635+268G>A		intron_variant	Intron 5 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.503+268G>A		intron_variant	Intron 11 of 22		NP_001341632.2
TF	NM_001354704.2	c.254+268G>A		intron_variant	Intron 4 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.635+268G>A		intron_variant	Intron 5 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000493011.5	n.951G>A		non_coding_transcript_exon_variant	Exon 5 of 5	2
TF	ENST00000482271.5	c.254+268G>A		intron_variant	Intron 4 of 5	4		ENSP00000419338.1
TF	ENST00000485977.1	n.158-1169G>A		intron_variant	Intron 2 of 4	3		ENSP00000418716.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19580 AN: 151870 Hom.: 1441 Cov.: 31

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.154 AC: 59433 AN: 384688 Hom.: 4897 Cov.: 3 AF XY: 0.152 AC XY: 31161 AN XY: 204588

African (AFR) AF: 0.0665 AC: 736 AN: 11074

American (AMR) AF: 0.136 AC: 2216 AN: 16344

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 2191 AN: 11528

East Asian (EAS) AF: 0.188 AC: 4580 AN: 24306

South Asian (SAS) AF: 0.103 AC: 4621 AN: 44858

European-Finnish (FIN) AF: 0.104 AC: 2360 AN: 22790

Middle Eastern (MID) AF: 0.178 AC: 288 AN: 1614

European-Non Finnish (NFE) AF: 0.170 AC: 39041 AN: 230186

Other (OTH) AF: 0.155 AC: 3400 AN: 21988

GnomAD4 genome AF: 0.129 AC: 19590 AN: 151990 Hom.: 1442 Cov.: 31 AF XY: 0.127 AC XY: 9457 AN XY: 74268

African (AFR) AF: 0.0617 AC: 2560 AN: 41482

American (AMR) AF: 0.139 AC: 2117 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3468

East Asian (EAS) AF: 0.193 AC: 993 AN: 5146

South Asian (SAS) AF: 0.104 AC: 496 AN: 4792

European-Finnish (FIN) AF: 0.0912 AC: 965 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11258 AN: 67942

Other (OTH) AF: 0.143 AC: 303 AN: 2112

Alfa AF: 0.0858 Hom.: 224

Bravo AF: 0.131

Asia WGS AF: 0.122 AC: 427 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	0.089
DANN	Benign	0.44
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3811657; hg19: chr3-133474607; COSMIC: COSV53923577; COSMIC: COSV53923577;