14-70023317-C-T

Variant names:

• chr14-70023317-C-T
• rs11846426
• NM_001034852.3:c.1161C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000361956.8(SMOC1):​c.1161C>T​(p.Phe387Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,182 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (9 hom., cov: 31)
  • Exomes 𝑓: 0.00065 (16 hom.)
• Consequence: SMOC1 ENST00000361956.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.29
• Publications: 1 publications found

Genes affected

SMOC1 (HGNC:20318): (SPARC related modular calcium binding 1) This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

SMOC1 Gene-Disease associations (from GenCC):

• microphthalmia with limb anomalies

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 14-70023317-C-T is Benign according to our data. Variant chr14-70023317-C-T is described in ClinVar as Benign. ClinVar VariationId is 257187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00689 (1049/152292) while in subpopulation AFR AF = 0.0235 (978/41556). AF 95% confidence interval is 0.0223. There are 9 homozygotes in GnomAd4. There are 492 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361956.8. 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
	SMOC1	NM_001034852.3	MANE Select	c.1161C>T	p.Phe387Phe	synonymous	Exon 11 of 12	NP_001030024.1
	SMOC1	NM_001425244.1		c.1194C>T	p.Phe398Phe	synonymous	Exon 11 of 12	NP_001412173.1
	SMOC1	NM_001425245.1		c.1194C>T	p.Phe398Phe	synonymous	Exon 11 of 12	NP_001412174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.1161C>T	p.Phe387Phe	synonymous	Exon 11 of 12	ENSP00000355110.4
	SMOC1	ENST00000381280.4	TSL:1	c.1161C>T	p.Phe387Phe	synonymous	Exon 11 of 12	ENSP00000370680.4

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1046 AN: 152174 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00169 AC: 424 AN: 251392 AF XY: 0.00139

Gnomad AFR exome AF: 0.0241

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000652 AC: 953 AN: 1461890 Hom.: 16 Cov.: 32 AF XY: 0.000606 AC XY: 441 AN XY: 727246

African (AFR) AF: 0.0245 AC: 820 AN: 33480

American (AMR) AF: 0.000894 AC: 40 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1112010

Other (OTH) AF: 0.00118 AC: 71 AN: 60394

GnomAD4 genome AF: 0.00689 AC: 1049 AN: 152292 Hom.: 9 Cov.: 31 AF XY: 0.00661 AC XY: 492 AN XY: 74468

African (AFR) AF: 0.0235 AC: 978 AN: 41556

American (AMR) AF: 0.00346 AC: 53 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00286 Hom.: 5

Bravo AF: 0.00794

Asia WGS AF: 0.000866 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs11846426; hg19: chr14-70490034;