rs57609901

Variant names:

• chr14-70011466-C-A
• rs57609901
• NM_001034852.3:c.858-19C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-70011466-C-A
• chr14-70011466-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001034852.3(SMOC1):​c.858-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,561,566 control chromosomes in the GnomAD database, including 35,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2679 hom., cov: 30)
  • Exomes 𝑓: 0.20 (32564 hom.)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.735
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-70011466-C-A is Benign according to our data. Variant chr14-70011466-C-A is described in ClinVar as Benign. ClinVar VariationId is 257190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC1	NM_001034852.3	c.858-19C>A		intron_variant	Intron 8 of 11	ENST00000361956.8	NP_001030024.1
SMOC1	NM_001425244.1	c.891-19C>A		intron_variant	Intron 8 of 11		NP_001412173.1
SMOC1	NM_001425245.1	c.891-19C>A		intron_variant	Intron 8 of 11		NP_001412174.1
SMOC1	NM_022137.6	c.858-19C>A		intron_variant	Intron 8 of 11		NP_071420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8	c.858-19C>A		intron_variant	Intron 8 of 11	1	NM_001034852.3	ENSP00000355110.4
SMOC1	ENST00000381280.4	c.858-19C>A		intron_variant	Intron 8 of 11	1		ENSP00000370680.4
SMOC1	ENST00000557483.1	n.436-19C>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24138 AN: 150564 Hom.: 2672 Cov.: 30

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.211 AC: 52951 AN: 251110 AF XY: 0.208

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.411

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.200 AC: 282363 AN: 1410884 Hom.: 32564 Cov.: 28 AF XY: 0.200 AC XY: 140833 AN XY: 704368

African (AFR) AF: 0.0349 AC: 1130 AN: 32418

American (AMR) AF: 0.337 AC: 15054 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3853 AN: 25688

East Asian (EAS) AF: 0.411 AC: 16227 AN: 39510

South Asian (SAS) AF: 0.204 AC: 17415 AN: 85370

European-Finnish (FIN) AF: 0.170 AC: 9023 AN: 53070

Middle Eastern (MID) AF: 0.110 AC: 623 AN: 5664

European-Non Finnish (NFE) AF: 0.195 AC: 207514 AN: 1065828

Other (OTH) AF: 0.196 AC: 11524 AN: 58728

GnomAD4 genome AF: 0.160 AC: 24148 AN: 150682 Hom.: 2679 Cov.: 30 AF XY: 0.166 AC XY: 12198 AN XY: 73484

African (AFR) AF: 0.0410 AC: 1693 AN: 41268

American (AMR) AF: 0.275 AC: 4160 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 503 AN: 3450

East Asian (EAS) AF: 0.404 AC: 2046 AN: 5070

South Asian (SAS) AF: 0.211 AC: 1003 AN: 4746

European-Finnish (FIN) AF: 0.191 AC: 1951 AN: 10202

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12282 AN: 67516

Other (OTH) AF: 0.174 AC: 361 AN: 2080

Alfa AF: 0.165 Hom.: 453

Bravo AF: 0.162

Asia WGS AF: 0.254 AC: 880 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microphthalmia with limb anomalies Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.46
DANN	Benign	0.66
PhyloP100		-0.73
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: rs57609901; hg19: chr14-70478183; COSMIC: COSV62759403;