14-35071558-G-T

Variant names:

• chr14-35071558-G-T
• rs17595975
• NM_173607.5:c.340-5592G>T

Variant summary

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

The NM_173607.5(FAM177A1):​c.340-5592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 150,902 control chromosomes in the GnomAD database, including 492 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 0.071 (492 hom., cov: 31)
• Consequence: FAM177A1 NM_173607.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 3 publications found

Genes affected

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

FAM177A1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173607.5. 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
	FAM177A1	NM_173607.5	MANE Select	c.340-5592G>T		intron	N/A	NP_775878.2
	FAM177A1	NM_001079519.1		c.271-5592G>T		intron	N/A	NP_001072987.1
	FAM177A1	NM_001289022.3		c.271-5592G>T		intron	N/A	NP_001275951.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM177A1	ENST00000280987.9	TSL:1 MANE Select	c.340-5592G>T		intron	N/A	ENSP00000280987.4
	FAM177A1	ENST00000382406.7	TSL:1	c.271-5592G>T		intron	N/A	ENSP00000371843.3
	FAM177A1	ENST00000555211.6	TSL:4	c.271-5592G>T		intron	N/A	ENSP00000451508.2

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10692 AN: 150784 Hom.: 493 Cov.: 31

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.0683

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0676

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

GnomAD4 genome AF: 0.0708 AC: 10687 AN: 150902 Hom.: 492 Cov.: 31 AF XY: 0.0685 AC XY: 5044 AN XY: 73678

African (AFR) AF: 0.0178 AC: 735 AN: 41180

American (AMR) AF: 0.0687 AC: 1031 AN: 15018

Ashkenazi Jewish (ASJ) AF: 0.0672 AC: 232 AN: 3452

East Asian (EAS) AF: 0.00137 AC: 7 AN: 5098

South Asian (SAS) AF: 0.0998 AC: 472 AN: 4728

European-Finnish (FIN) AF: 0.0537 AC: 558 AN: 10382

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7421 AN: 67750

Other (OTH) AF: 0.0664 AC: 139 AN: 2092

Alfa AF: 0.0929 Hom.: 352

Bravo AF: 0.0685

Asia WGS AF: 0.0460 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.38
PhyloP100		0.038
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: rs17595975; hg19: chr14-35540764;