rs12234571

Variant names:

• chr7-77920589-T-G
• rs12234571
• ENST00000248550.7:c.963+124T>G

Variant summary

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

The ENST00000248550.7(PHTF2):​c.963+124T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 692,402 control chromosomes in the GnomAD database, including 3,252 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 0.10 (1080 hom., cov: 33)
  • Exomes 𝑓: 0.076 (2172 hom.)
• Consequence: PHTF2 ENST00000248550.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 7 publications found

Genes affected

PHTF2 (HGNC:13411): (putative homeodomain transcription factor 2) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHTF2	NM_001366089.1	c.963+124T>G		intron_variant	Intron 9 of 18		NP_001353018.1
PHTF2	NM_001127357.2	c.861+124T>G		intron_variant	Intron 8 of 17		NP_001120829.1
PHTF2	NM_001395272.1	c.861+124T>G		intron_variant	Intron 9 of 18		NP_001382201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHTF2	ENST00000422959.8	c.861+124T>G		intron_variant	Intron 9 of 18	5		ENSP00000403042.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15453 AN: 152190 Hom.: 1077 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0764 AC: 41244 AN: 540094 Hom.: 2172 AF XY: 0.0818 AC XY: 23894 AN XY: 292006

African (AFR) AF: 0.192 AC: 2611 AN: 13572

American (AMR) AF: 0.0733 AC: 1326 AN: 18102

Ashkenazi Jewish (ASJ) AF: 0.0728 AC: 1302 AN: 17880

East Asian (EAS) AF: 0.104 AC: 3284 AN: 31562

South Asian (SAS) AF: 0.181 AC: 9738 AN: 53838

European-Finnish (FIN) AF: 0.0286 AC: 1162 AN: 40676

Middle Eastern (MID) AF: 0.101 AC: 367 AN: 3644

European-Non Finnish (NFE) AF: 0.0574 AC: 19023 AN: 331204

Other (OTH) AF: 0.0821 AC: 2431 AN: 29616

GnomAD4 genome AF: 0.102 AC: 15476 AN: 152308 Hom.: 1080 Cov.: 33 AF XY: 0.102 AC XY: 7632 AN XY: 74492

African (AFR) AF: 0.188 AC: 7810 AN: 41546

American (AMR) AF: 0.0849 AC: 1299 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3472

East Asian (EAS) AF: 0.110 AC: 573 AN: 5186

South Asian (SAS) AF: 0.188 AC: 909 AN: 4830

European-Finnish (FIN) AF: 0.0279 AC: 297 AN: 10628

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0580 AC: 3948 AN: 68032

Other (OTH) AF: 0.108 AC: 228 AN: 2112

Alfa AF: 0.0820 Hom.: 1030

Bravo AF: 0.108

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-1.3
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: rs12234571; hg19: chr7-77549906; COSMIC: COSV107215938;