4-88855930-A-G

Variant summary

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

The NM_014883.4(FAM13A):c.844-4747T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,988 control chromosomes in the GnomAD database, including 11,234 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 0.38 (11234 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM13A NM_014883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

Genes affected

FAM13A (HGNC:19367): (family with sequence similarity 13 member A) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Implicated in chronic obstructive pulmonary disease. [provided by Alliance of Genome Resources, Apr 2022]

LOC124900732 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM13A	NM_014883.4	c.844-4747T>C		intron_variant		ENST00000264344.10
LOC124900732	XR_007058189.1	n.7883T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM13A	ENST00000264344.10	c.844-4747T>C		intron_variant		5	NM_014883.4	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57737 AN: 151870 Hom.: 11202 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.360

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.380 AC: 57804 AN: 151988 Hom.: 11234 Cov.: 32 AF XY: 0.381 AC XY: 28313 AN XY: 74284

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.368

Alfa AF: 0.346 Hom.: 18926

Bravo AF: 0.391

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.95
Dann	Benign	0.59

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: rs6830970; hg19: chr4-89777081;