15-92635945-T-C

Position:

• chr15-92635945-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000327355.6(FAM174B):​c.345-5600A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,042 control chromosomes in the GnomAD database, including 2,219 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 0.17 (2219 hom., cov: 31)
• Consequence: FAM174B ENST00000327355.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.89

Genes affected

FAM174B (HGNC:34339): (family with sequence similarity 174 member B) Involved in Golgi organization. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM174B	NM_207446.3	c.345-5600A>G		intron_variant		ENST00000327355.6	NP_997329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM174B	ENST00000327355.6	c.345-5600A>G		intron_variant		1	NM_207446.3	ENSP00000329040	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25220 AN: 151924 Hom.: 2221 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.166 AC: 25216 AN: 152042 Hom.: 2219 Cov.: 31 AF XY: 0.163 AC XY: 12078 AN XY: 74322

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.151

Alfa AF: 0.188 Hom.: 6146

Bravo AF: 0.164

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.15
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs285757; hg19: chr15-93179175;