rs3766186

Variant names:

• chr1-1227055-C-A
• rs3766186
• NM_016176.6:c.305+1413G>T

Variant summary

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

The NM_016176.6(SDF4):​c.305+1413G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,212 control chromosomes in the GnomAD database, including 1,138 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 0.11 (1138 hom., cov: 33)
• Consequence: SDF4 NM_016176.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 16 publications found

Genes affected

SDF4 (HGNC:24188): (stromal cell derived factor 4) This gene encodes a stromal cell derived factor that is a member of the CREC protein family. The encoded protein contains six EF-hand motifs and calcium-binding motifs. This protein localizes to the Golgi lumen and may be involved in regulating calcium dependent cellular activities. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDF4	NM_016176.6	c.305+1413G>T		intron_variant	Intron 2 of 6	ENST00000360001.12	NP_057260.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDF4	ENST00000360001.12	c.305+1413G>T		intron_variant	Intron 2 of 6	1	NM_016176.6	ENSP00000353094.7

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17387 AN: 152094 Hom.: 1132 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.114 AC: 17396 AN: 152212 Hom.: 1138 Cov.: 33 AF XY: 0.115 AC XY: 8593 AN XY: 74428

African (AFR) AF: 0.168 AC: 6993 AN: 41512

American (AMR) AF: 0.0680 AC: 1041 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 266 AN: 3472

East Asian (EAS) AF: 0.174 AC: 900 AN: 5176

South Asian (SAS) AF: 0.0949 AC: 458 AN: 4826

European-Finnish (FIN) AF: 0.0937 AC: 995 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0943 AC: 6414 AN: 67990

Other (OTH) AF: 0.100 AC: 212 AN: 2110

Alfa AF: 0.0993 Hom.: 470

Bravo AF: 0.116

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3766186; hg19: chr1-1162435;