chr1-1220751-T-C

Variant names:

• chr1-1220751-T-C
• rs2887286
• NM_016176.6:c.557-1824A>G

Variant summary

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

The NM_016176.6(SDF4):​c.557-1824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,288,494 control chromosomes in the GnomAD database, including 46,944 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 0.31 (10080 hom., cov: 34)
  • Exomes 𝑓: 0.22 (36864 hom.)
• Consequence: SDF4 NM_016176.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 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.557-1824A>G		intron	N/A	NP_057260.3
	SDF4	NM_016547.3		c.557-1824A>G		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.557-1824A>G		intron	N/A	ENSP00000353094.7
	SDF4	ENST00000263741.12	TSL:1	c.557-1824A>G		intron	N/A	ENSP00000263741.8
	SDF4	ENST00000900950.1		c.557-1824A>G		intron	N/A	ENSP00000571009.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47478 AN: 151878 Hom.: 10048 Cov.: 34

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.300

GnomAD2 exomes AF: 0.368 AC: 47149 AN: 128100 AF XY: 0.366

Gnomad AFR exome AF: 0.486

Gnomad AMR exome AF: 0.539

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.844

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.217 AC: 246972 AN: 1136498 Hom.: 36864 Cov.: 35 AF XY: 0.226 AC XY: 125990 AN XY: 557538

African (AFR) AF: 0.479 AC: 11683 AN: 24396

American (AMR) AF: 0.535 AC: 15130 AN: 28256

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 2572 AN: 15934

East Asian (EAS) AF: 0.839 AC: 10777 AN: 12838

South Asian (SAS) AF: 0.500 AC: 38079 AN: 76182

European-Finnish (FIN) AF: 0.175 AC: 2220 AN: 12650

Middle Eastern (MID) AF: 0.204 AC: 895 AN: 4392

European-Non Finnish (NFE) AF: 0.168 AC: 154726 AN: 920344

Other (OTH) AF: 0.262 AC: 10890 AN: 41506

GnomAD4 genome AF: 0.313 AC: 47559 AN: 151996 Hom.: 10080 Cov.: 34 AF XY: 0.321 AC XY: 23823 AN XY: 74304

African (AFR) AF: 0.482 AC: 19964 AN: 41438

American (AMR) AF: 0.432 AC: 6601 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3466

East Asian (EAS) AF: 0.835 AC: 4319 AN: 5172

South Asian (SAS) AF: 0.528 AC: 2548 AN: 4822

European-Finnish (FIN) AF: 0.171 AC: 1803 AN: 10554

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10932 AN: 67948

Other (OTH) AF: 0.307 AC: 648 AN: 2114

Alfa AF: 0.211 Hom.: 9179

Bravo AF: 0.336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		0.047
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2887286; hg19: chr1-1156131;