chr6-47973528-A-G

Variant names:

• chr6-47973528-A-G
• rs2814478
• NM_001384253.1:c.898+35106T>C

Variant summary

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

The NM_001384253.1(PTCHD4):​c.898+35106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 152,316 control chromosomes in the GnomAD database, including 71,696 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 0.97 (71696 hom., cov: 32)
• Consequence: PTCHD4 NM_001384253.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 2 publications found

Genes affected

PTCHD4 (HGNC:21345): (patched domain containing 4) Predicted to be integral component of membrane. Predicted to be active in membrane. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384253.1. 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
	PTCHD4	NM_001384253.1	MANE Select	c.898+35106T>C		intron	N/A	NP_001371182.1
	PTCHD4	NM_001013732.4		c.907+35106T>C		intron	N/A	NP_001013754.3
	PTCHD4	NM_207499.2		c.907+35106T>C		intron	N/A	NP_997382.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCHD4	ENST00000339488.9	TSL:2 MANE Select	c.898+35106T>C		intron	N/A	ENSP00000341914.5
	PTCHD4	ENST00000398738.3	TSL:1	c.898+35106T>C		intron	N/A	ENSP00000381722.3
	PTCHD4	ENST00000679966.1		c.1072+35106T>C		intron	N/A	ENSP00000506133.1

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147667 AN: 152200 Hom.: 71643 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.964

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

GnomAD4 genome AF: 0.970 AC: 147778 AN: 152316 Hom.: 71696 Cov.: 32 AF XY: 0.970 AC XY: 72213 AN XY: 74482

African (AFR) AF: 0.975 AC: 40540 AN: 41576

American (AMR) AF: 0.959 AC: 14674 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3318 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5168

South Asian (SAS) AF: 0.996 AC: 4809 AN: 4830

European-Finnish (FIN) AF: 0.961 AC: 10195 AN: 10614

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65847 AN: 68038

Other (OTH) AF: 0.964 AC: 2036 AN: 2112

Alfa AF: 0.971 Hom.: 26695

Bravo AF: 0.969

Asia WGS AF: 0.994 AC: 3456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.072
DANN	Benign	0.33
PhyloP100		-1.4
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: rs2814478; hg19: chr6-47941264;