14-69989982-T-G

Variant names:

• chr14-69989982-T-G
• rs227425
• NM_001034852.3:c.527-2435T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001034852.3(SMOC1):​c.527-2435T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,100 control chromosomes in the GnomAD database, including 21,125 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 0.52 (21125 hom., cov: 33)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 21 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC1	NM_001034852.3	c.527-2435T>G		intron_variant	Intron 5 of 11	ENST00000361956.8	NP_001030024.1
SMOC1	NM_001425244.1	c.527-2402T>G		intron_variant	Intron 5 of 11		NP_001412173.1
SMOC1	NM_001425245.1	c.527-2402T>G		intron_variant	Intron 5 of 11		NP_001412174.1
SMOC1	NM_022137.6	c.527-2435T>G		intron_variant	Intron 5 of 11		NP_071420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8	c.527-2435T>G		intron_variant	Intron 5 of 11	1	NM_001034852.3	ENSP00000355110.4
SMOC1	ENST00000381280.4	c.527-2435T>G		intron_variant	Intron 5 of 11	1		ENSP00000370680.4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79339 AN: 151982 Hom.: 21097 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.524

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.522 AC: 79426 AN: 152100 Hom.: 21125 Cov.: 33 AF XY: 0.524 AC XY: 38954 AN XY: 74364

African (AFR) AF: 0.590 AC: 24469 AN: 41490

American (AMR) AF: 0.520 AC: 7948 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1588 AN: 3472

East Asian (EAS) AF: 0.437 AC: 2255 AN: 5162

South Asian (SAS) AF: 0.342 AC: 1646 AN: 4816

European-Finnish (FIN) AF: 0.594 AC: 6290 AN: 10584

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33680 AN: 67982

Other (OTH) AF: 0.519 AC: 1096 AN: 2110

Alfa AF: 0.492 Hom.: 23269

Bravo AF: 0.520

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.77
PhyloP100		1.9
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: rs227425; hg19: chr14-70456699;