rs17618203

Variant names:

• chr16-67113107-G-A
• rs17618203
• NM_025187.5:c.64+2868G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_025187.5(PHAF1):​c.64+2868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,330 control chromosomes in the GnomAD database, including 58 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 0.024 (58 hom., cov: 31)
• Consequence: PHAF1 NM_025187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783
• Publications: 8 publications found

Genes affected

PHAF1 (HGNC:29564): (phagosome assembly factor 1) Predicted to be involved in Golgi to plasma membrane protein transport. Located in phagophore assembly site. [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=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0237 (3606/152330) while in subpopulation NFE AF = 0.0327 (2223/68038). AF 95% confidence interval is 0.0315. There are 58 homozygotes in GnomAd4. There are 1716 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025187.5. 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
	PHAF1	NM_025187.5	MANE Select	c.64+2868G>A		intron	N/A	NP_079463.2
	PHAF1	NM_001320540.2		c.64+2868G>A		intron	N/A	NP_001307469.1
	PHAF1	NM_001320541.2		c.64+2868G>A		intron	N/A	NP_001307470.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHAF1	ENST00000219139.8	TSL:1 MANE Select	c.64+2868G>A		intron	N/A	ENSP00000219139.3
	PHAF1	ENST00000569600.5	TSL:1	c.64+2868G>A		intron	N/A	ENSP00000455182.1
	PHAF1	ENST00000563853.6	TSL:3	c.64+2868G>A		intron	N/A	ENSP00000456688.2

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3600 AN: 152212 Hom.: 58 Cov.: 31

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0237 AC: 3606 AN: 152330 Hom.: 58 Cov.: 31 AF XY: 0.0230 AC XY: 1716 AN XY: 74490

African (AFR) AF: 0.00606 AC: 252 AN: 41574

American (AMR) AF: 0.0322 AC: 493 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.0162 AC: 84 AN: 5186

South Asian (SAS) AF: 0.0302 AC: 146 AN: 4828

European-Finnish (FIN) AF: 0.0172 AC: 183 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0327 AC: 2223 AN: 68038

Other (OTH) AF: 0.0284 AC: 60 AN: 2112

Alfa AF: 0.0280 Hom.: 10

Bravo AF: 0.0249

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.70
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism

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: rs17618203; hg19: chr16-67147010;