rs277606

Variant names:

• chr9-34785311-T-C
• rs277606
• ENST00000837930.1:n.174+82273T>C

Variant summary

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

The ENST00000837930.1(ENSG00000230074):​n.174+82273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,094 control chromosomes in the GnomAD database, including 22,520 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 0.51 (22520 hom., cov: 32)
• Consequence: ENSG00000230074 ENST00000837930.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.891
• Publications: 8 publications found

Genes affected

ENSG00000230074 (HGNC:):

PHF24 (HGNC:29180): (PHD finger protein 24) Predicted to enable metal ion binding activity. Predicted to act upstream of or within several processes, including detection of mechanical stimulus involved in sensory perception of pain; gamma-aminobutyric acid signaling pathway; and regulation of GABAergic synaptic transmission. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF24	XM_047423102.1	c.133+82273T>C		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1	c.70+82273T>C		intron_variant	Intron 2 of 9		XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000230074	ENST00000837930.1	n.174+82273T>C		intron_variant	Intron 2 of 3
ENSG00000230074	ENST00000837931.1	n.306+82273T>C		intron_variant	Intron 2 of 3
ENSG00000230074	ENST00000837932.1	n.138+82273T>C		intron_variant	Intron 2 of 3
ENSG00000230074	ENST00000837939.1	n.193-1623T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78064 AN: 151976 Hom.: 22514 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.513 AC: 78080 AN: 152094 Hom.: 22520 Cov.: 32 AF XY: 0.513 AC XY: 38163 AN XY: 74354

African (AFR) AF: 0.248 AC: 10306 AN: 41508

American (AMR) AF: 0.584 AC: 8939 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1990 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1626 AN: 5174

South Asian (SAS) AF: 0.473 AC: 2279 AN: 4814

European-Finnish (FIN) AF: 0.677 AC: 7149 AN: 10560

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43912 AN: 67954

Other (OTH) AF: 0.560 AC: 1183 AN: 2112

Alfa AF: 0.612 Hom.: 48815

Bravo AF: 0.498

Asia WGS AF: 0.386 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.59
PhyloP100		0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs277606; hg19: chr9-34785308;