rs1187415

Variant names:

• chr12-124006982-G-C
• rs1187415
• NM_152437.3:c.-660-4399G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-124006982-G-C
• chr12-124006982-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152437.3(ZNF664):​c.-660-4399G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,000 control chromosomes in the GnomAD database, including 29,566 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 0.61 (29566 hom., cov: 31)
• Consequence: ZNF664 NM_152437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 25 publications found

Genes affected

ZNF664 (HGNC:25406): (zinc finger protein 664) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF664	NM_152437.3	c.-660-4399G>C		intron_variant	Intron 3 of 4	ENST00000337815.9	NP_689650.1
ZNF664	NM_001204298.2	c.-660-4399G>C		intron_variant	Intron 3 of 4		NP_001191227.1
ZNF664-RFLNA	NM_001204299.3	c.-234+32962G>C		intron_variant	Intron 2 of 4		NP_001191228.1
ZNF664-RFLNA	NM_001347902.2	c.-234+32962G>C		intron_variant	Intron 2 of 4		NP_001334831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF664	ENST00000337815.9	c.-660-4399G>C		intron_variant	Intron 3 of 4	1	NM_152437.3	ENSP00000337320.4

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92839 AN: 151882 Hom.: 29560 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.611 AC: 92882 AN: 152000 Hom.: 29566 Cov.: 31 AF XY: 0.621 AC XY: 46129 AN XY: 74290

African (AFR) AF: 0.431 AC: 17862 AN: 41448

American (AMR) AF: 0.672 AC: 10254 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1954 AN: 3466

East Asian (EAS) AF: 0.907 AC: 4683 AN: 5164

South Asian (SAS) AF: 0.784 AC: 3779 AN: 4822

European-Finnish (FIN) AF: 0.719 AC: 7592 AN: 10558

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44754 AN: 67962

Other (OTH) AF: 0.604 AC: 1271 AN: 2104

Alfa AF: 0.628 Hom.: 3654

Bravo AF: 0.595

Asia WGS AF: 0.768 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.50
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1187415; hg19: chr12-124491529;