15-59372946-C-A

Position:

• chr15-59372946-C-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The ENST00000558348.5(FAM81A):​c.-161+167C>A variant causes a intron change. The variant allele was found at a frequency of 0.075 in 164,056 control chromosomes in the GnomAD database, including 1,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (1057 hom., cov: 31)
  • Exomes 𝑓: 0.030 (15 hom.)
• Consequence: FAM81A ENST00000558348.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.80

Genes affected

FAM81A (HGNC:28379): (family with sequence similarity 81 member A)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.11).
• BP6: Variant 15-59372946-C-A is Benign according to our data. Variant chr15-59372946-C-A is described in ClinVar as [Benign]. Clinvar id is 1243001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.59372946C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM81A	ENST00000558348.5	c.-161+167C>A		intron_variant		4		ENSP00000453918.1
FAM81A	ENST00000560394.5	c.-306C>A		upstream_gene_variant		4		ENSP00000452962.1

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11923 AN: 152130 Hom.: 1051 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0728

GnomAD4 exome AF: 0.0302 AC: 356 AN: 11806 Hom.: 15 Cov.: 0 AF XY: 0.0271 AC XY: 165 AN XY: 6078

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.0391

Gnomad4 ASJ exome AF: 0.0611

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.00769

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0623

GnomAD4 genome AF: 0.0785 AC: 11954 AN: 152250 Hom.: 1057 Cov.: 31 AF XY: 0.0761 AC XY: 5662 AN XY: 74450

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0389

Gnomad4 FIN AF: 0.00518

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0558 Hom.: 71

Bravo AF: 0.0866

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 29, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113915226; hg19: chr15-59665145;