rs4765078

Variant names:

• chr12-124162281-T-C
• rs4765078
• NM_001204299.3:c.-37+12490T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204299.3. 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
	ZNF664-RFLNA	NM_001204299.3		c.-37+12490T>C		intron	N/A	NP_001191228.1
	ZNF664-RFLNA	NM_001347902.2		c.-37+12490T>C		intron	N/A	NP_001334831.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFLNA	ENST00000389727.8	TSL:5	c.-37+12490T>C		intron	N/A	ENSP00000374377.4
	RFLNA	ENST00000545615.1	TSL:3	n.391+12490T>C		intron	N/A

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

African (AFR) AF: 0.624 AC: 25869 AN: 41464

American (AMR) AF: 0.420 AC: 6422 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1465 AN: 3466

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5168

South Asian (SAS) AF: 0.526 AC: 2534 AN: 4818

European-Finnish (FIN) AF: 0.337 AC: 3566 AN: 10590

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25467 AN: 67976

Other (OTH) AF: 0.430 AC: 906 AN: 2106

Alfa AF: 0.399 Hom.: 21423

Bravo AF: 0.456

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.64
PhyloP100		-0.056

Splicing

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

Other links and lift over

dbSNP: rs4765078; hg19: chr12-124646827;