chr14-69899207-A-C

Variant names:

• chr14-69899207-A-C
• rs11627546
• NM_001034852.3:c.99+19430A>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.99+19430A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,114 control chromosomes in the GnomAD database, including 39,043 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 0.67 (39043 hom., cov: 32)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC1	NM_001034852.3	c.99+19430A>C		intron_variant	Intron 1 of 11	ENST00000361956.8	NP_001030024.1
SMOC1	NM_001425244.1	c.99+19430A>C		intron_variant	Intron 1 of 11		NP_001412173.1
SMOC1	NM_001425245.1	c.99+19430A>C		intron_variant	Intron 1 of 11		NP_001412174.1
SMOC1	NM_022137.6	c.99+19430A>C		intron_variant	Intron 1 of 11		NP_071420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8	c.99+19430A>C		intron_variant	Intron 1 of 11	1	NM_001034852.3	ENSP00000355110.4
SMOC1	ENST00000381280.4	c.99+19430A>C		intron_variant	Intron 1 of 11	1		ENSP00000370680.4
SMOC1	ENST00000555917.1	n.404+34993A>C		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102154 AN: 151996 Hom.: 39037 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.672 AC: 102187 AN: 152114 Hom.: 39043 Cov.: 32 AF XY: 0.679 AC XY: 50467 AN XY: 74364

African (AFR) AF: 0.277 AC: 11486 AN: 41464

American (AMR) AF: 0.776 AC: 11864 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2672 AN: 3468

East Asian (EAS) AF: 0.913 AC: 4737 AN: 5186

South Asian (SAS) AF: 0.766 AC: 3682 AN: 4804

European-Finnish (FIN) AF: 0.867 AC: 9189 AN: 10598

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56201 AN: 67996

Other (OTH) AF: 0.693 AC: 1462 AN: 2110

Alfa AF: 0.693 Hom.: 34287

Bravo AF: 0.648

Asia WGS AF: 0.786 AC: 2729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.77
PhyloP100		-0.014
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

Publications

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Other links and lift over

dbSNP: rs11627546; hg19: chr14-70365924;