chr4-48617920-C-T

Position:

• chr4-48617920-C-T

Variant summary

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

The NM_015030.2(FRYL):​c.411+1354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,036 control chromosomes in the GnomAD database, including 22,179 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 0.53 (22175 hom., cov: 31)
  • Exomes 𝑓: 0.57 (4 hom.)
• Consequence: FRYL NM_015030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

Genes affected

FRYL (HGNC:29127): (FRY like transcription coactivator) Predicted to be involved in cell morphogenesis and neuron projection development. Predicted to be active in cell cortex and site of polarized growth. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRYL	NM_015030.2	c.411+1354G>A		intron_variant		ENST00000358350.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRYL	ENST00000358350.9	c.411+1354G>A		intron_variant		5	NM_015030.2	A1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80623 AN: 151890 Hom.: 22155 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.571 AC: 16 AN: 28 Hom.: 4 Cov.: 0 AF XY: 0.591 AC XY: 13 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.636

GnomAD4 genome AF: 0.531 AC: 80684 AN: 152008 Hom.: 22175 Cov.: 31 AF XY: 0.528 AC XY: 39224 AN XY: 74288

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.486

Alfa AF: 0.523 Hom.: 3592

Bravo AF: 0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.44

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: rs6843340; hg19: chr4-48619937;