chr14-69990936-A-C

Variant names:

• chr14-69990936-A-C
• rs227422
• NM_001034852.3:c.527-1481A>C

Variant summary

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

The NM_001034852.3(SMOC1):​c.527-1481A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,474 control chromosomes in the GnomAD database, including 15,974 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 0.44 (15974 hom., cov: 31)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC1	NM_001034852.3	c.527-1481A>C		intron_variant	Intron 5 of 11	ENST00000361956.8	NP_001030024.1
SMOC1	NM_001425244.1	c.527-1448A>C		intron_variant	Intron 5 of 11		NP_001412173.1
SMOC1	NM_001425245.1	c.527-1448A>C		intron_variant	Intron 5 of 11		NP_001412174.1
SMOC1	NM_022137.6	c.527-1481A>C		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.527-1481A>C		intron_variant	Intron 5 of 11	1	NM_001034852.3	ENSP00000355110.4
SMOC1	ENST00000381280.4	c.527-1481A>C		intron_variant	Intron 5 of 11	1		ENSP00000370680.4

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66637 AN: 151356 Hom.: 15949 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.440 AC: 66718 AN: 151474 Hom.: 15974 Cov.: 31 AF XY: 0.439 AC XY: 32468 AN XY: 74000

African (AFR) AF: 0.629 AC: 25909 AN: 41196

American (AMR) AF: 0.436 AC: 6644 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1108 AN: 3458

East Asian (EAS) AF: 0.437 AC: 2242 AN: 5136

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4814

European-Finnish (FIN) AF: 0.415 AC: 4346 AN: 10482

Middle Eastern (MID) AF: 0.355 AC: 103 AN: 290

European-Non Finnish (NFE) AF: 0.355 AC: 24073 AN: 67852

Other (OTH) AF: 0.416 AC: 877 AN: 2106

Alfa AF: 0.362 Hom.: 3624

Bravo AF: 0.454

Asia WGS AF: 0.334 AC: 1162 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.34
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: rs227422; hg19: chr14-70457653;