rs28367033

Variant names:

• chr14-69952081-G-A
• rs28367033
• NM_001034852.3:c.100-57G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-69952081-G-A
• chr14-69952081-G-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.100-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,583,550 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (147 hom., cov: 32)
  • Exomes 𝑓: 0.014 (305 hom.)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.461
• 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, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-69952081-G-A is Benign according to our data. Variant chr14-69952081-G-A is described in ClinVar as Benign. ClinVar VariationId is 1222405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	NM_001034852.3	MANE Select	c.100-57G>A		intron	N/A	NP_001030024.1	Q9H4F8-2
	SMOC1	NM_001425244.1		c.100-57G>A		intron	N/A	NP_001412173.1
	SMOC1	NM_001425245.1		c.100-57G>A		intron	N/A	NP_001412174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.100-57G>A		intron	N/A	ENSP00000355110.4	Q9H4F8-2
	SMOC1	ENST00000381280.4	TSL:1	c.100-57G>A		intron	N/A	ENSP00000370680.4	Q9H4F8-1
	SMOC1	ENST00000853906.1		c.100-57G>A		intron	N/A	ENSP00000523965.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4940 AN: 152042 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0141 AC: 20202 AN: 1431390 Hom.: 305 AF XY: 0.0140 AC XY: 9977 AN XY: 713946

African (AFR) AF: 0.0837 AC: 2750 AN: 32862

American (AMR) AF: 0.0165 AC: 736 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0249 AC: 646 AN: 25974

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39462

South Asian (SAS) AF: 0.00708 AC: 605 AN: 85468

European-Finnish (FIN) AF: 0.00315 AC: 168 AN: 53300

Middle Eastern (MID) AF: 0.0947 AC: 540 AN: 5700

European-Non Finnish (NFE) AF: 0.0125 AC: 13526 AN: 1084560

Other (OTH) AF: 0.0207 AC: 1229 AN: 59388

GnomAD4 genome AF: 0.0325 AC: 4941 AN: 152160 Hom.: 147 Cov.: 32 AF XY: 0.0307 AC XY: 2283 AN XY: 74388

African (AFR) AF: 0.0803 AC: 3332 AN: 41486

American (AMR) AF: 0.0235 AC: 359 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4818

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10596

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1027 AN: 68002

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0239 Hom.: 24

Bravo AF: 0.0367

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.72
PhyloP100		-0.46
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: rs28367033; hg19: chr14-70418798;