rs4765078

chr12-124162281-T-C

Variant summary

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

The NM_001204299.3(ZNF664-RFLNA):c.-37+12490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,078 control chromosomes in the GnomAD database, including 16,112 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 0.45 (16112 hom., cov: 32)
• Consequence: ZNF664-RFLNA NM_001204299.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

Genes affected

ZNF664-RFLNA (HGNC:):

RFLNA (HGNC:27051): (refilin A) Predicted to enable filamin binding activity. Predicted to be involved in several processes, including actin filament bundle organization; negative regulation of bone mineralization involved in bone maturation; and negative regulation of chondrocyte development. Predicted to be located in cytoplasm. Predicted to be active in actin filament bundle. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF664-RFLNA	NM_001204299.3	c.-37+12490T>C		intron_variant
ZNF664-RFLNA	NM_001347902.2	c.-37+12490T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFLNA	ENST00000389727.8	c.-37+12490T>C		intron_variant		5
RFLNA	ENST00000545615.1	n.391+12490T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67782 AN: 151960 Hom.: 16099 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.446 AC: 67844 AN: 152078 Hom.: 16112 Cov.: 32 AF XY: 0.447 AC XY: 33220 AN XY: 74358

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.430

Alfa AF: 0.395 Hom.: 15970

Bravo AF: 0.456

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.0
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4765078; hg19: chr12-124646827;