rs7515488

Variant names:

• chr1-1228424-C-T
• rs7515488
• NM_016176.6:c.305+44G>A

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+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,537,778 control chromosomes in the GnomAD database, including 19,436 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 0.17 (2148 hom., cov: 34)
  • Exomes 𝑓: 0.16 (17288 hom.)
• Consequence: SDF4 NM_016176.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747
• Publications: 31 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016176.6. 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
	SDF4	NM_016176.6	MANE Select	c.305+44G>A		intron	N/A	NP_057260.3
	SDF4	NM_016547.3		c.305+44G>A		intron	N/A	NP_057631.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDF4	ENST00000360001.12	TSL:1 MANE Select	c.305+44G>A		intron	N/A	ENSP00000353094.7
	SDF4	ENST00000263741.12	TSL:1	c.305+44G>A		intron	N/A	ENSP00000263741.8
	SDF4	ENST00000403997.2	TSL:3	c.128+44G>A		intron	N/A	ENSP00000384207.2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 24868 AN: 148360 Hom.: 2137 Cov.: 34

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.173 AC: 27827 AN: 160762 AF XY: 0.171

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.267

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.156 AC: 217088 AN: 1389322 Hom.: 17288 Cov.: 30 AF XY: 0.156 AC XY: 106633 AN XY: 683452

African (AFR) AF: 0.213 AC: 6742 AN: 31682

American (AMR) AF: 0.147 AC: 5730 AN: 39066

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 2866 AN: 22450

East Asian (EAS) AF: 0.196 AC: 7413 AN: 37736

South Asian (SAS) AF: 0.158 AC: 11880 AN: 75328

European-Finnish (FIN) AF: 0.157 AC: 7279 AN: 46330

Middle Eastern (MID) AF: 0.170 AC: 932 AN: 5486

European-Non Finnish (NFE) AF: 0.154 AC: 164877 AN: 1073952

Other (OTH) AF: 0.164 AC: 9369 AN: 57292

GnomAD4 genome AF: 0.168 AC: 24913 AN: 148456 Hom.: 2148 Cov.: 34 AF XY: 0.170 AC XY: 12258 AN XY: 72290

African (AFR) AF: 0.206 AC: 8567 AN: 41556

American (AMR) AF: 0.144 AC: 1969 AN: 13640

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3464

East Asian (EAS) AF: 0.263 AC: 997 AN: 3786

South Asian (SAS) AF: 0.182 AC: 776 AN: 4254

European-Finnish (FIN) AF: 0.142 AC: 1498 AN: 10582

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10165 AN: 67884

Other (OTH) AF: 0.160 AC: 333 AN: 2084

Alfa AF: 0.152 Hom.: 4418

Bravo AF: 0.168

Asia WGS AF: 0.200 AC: 688 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.75
PhyloP100		0.75
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7515488; hg19: chr1-1163804; COSMIC: COSV55421149; COSMIC: COSV55421149;