3-133789620-A-T

Variant names:

• chr3-133789620-A-T
• rs1830084
• NM_001063.4:c.*11000A>T

Variant summary

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

The NM_001063.4(TF):​c.*11000A>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 0.29 in 152,174 control chromosomes in the GnomAD database, including 7,080 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 0.29 (7079 hom., cov: 33)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: TF NM_001063.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 25 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]

SRPRB (HGNC:24085): (SRP receptor subunit beta) The protein encoded by this gene has similarity to mouse protein which is a subunit of the signal recognition particle receptor (SR). This subunit is a transmembrane GTPase belonging to the GTPase superfamily. It anchors alpha subunit, a peripheral membrane GTPase, to the ER membrane. SR is required for the cotranslational targeting of both secretory and membrane proteins to the ER membrane. [provided by RefSeq, Jul 2008]

LOC105374116 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.*11000A>T		3_prime_UTR	Exon 17 of 17	NP_001054.2	P02787
	TF	NM_001354703.2		c.*11000A>T		3_prime_UTR	Exon 23 of 23	NP_001341632.2
	TF	NM_001354704.2		c.*11000A>T		3_prime_UTR	Exon 16 of 16	NP_001341633.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.*11000A>T		3_prime_UTR	Exon 17 of 17	ENSP00000385834.3	P02787
	SRPRB	ENST00000466490.7	TSL:5	c.-174+5476A>T		intron	N/A	ENSP00000418401.1	Q9Y5M8

Frequencies

GnomAD3 genomes AF: 0.289 AC: 44004 AN: 152036 Hom.: 7060 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.250 AC: 5 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 5 AN: 20

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.290 AC: 44053 AN: 152154 Hom.: 7079 Cov.: 33 AF XY: 0.292 AC XY: 21751 AN XY: 74386

African (AFR) AF: 0.162 AC: 6710 AN: 41508

American (AMR) AF: 0.385 AC: 5889 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 925 AN: 3472

East Asian (EAS) AF: 0.462 AC: 2391 AN: 5180

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4822

European-Finnish (FIN) AF: 0.273 AC: 2890 AN: 10578

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22311 AN: 67986

Other (OTH) AF: 0.300 AC: 634 AN: 2114

Alfa AF: 0.173 Hom.: 359

Bravo AF: 0.293

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.96
DANN	Benign	0.16
PhyloP100		-1.1
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: rs1830084; hg19: chr3-133508464;