rs11098451

Variant names:

• chr4-118796518-G-A
• rs11098451
• NM_014822.4:c.1041+1165C>T

Variant summary

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

The NM_014822.4(SEC24D):​c.1041+1165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 152,216 control chromosomes in the GnomAD database, including 384 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 0.066 (384 hom., cov: 32)
• Consequence: SEC24D NM_014822.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 5 publications found

Genes affected

SEC24D (HGNC:10706): (SEC24 homolog D, COPII coat complex component) The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec24p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. This gene product is implicated in the shaping of the vesicle, and also in cargo selection and concentration. Mutations in this gene have been associated with Cole-Carpenter syndrome, a disorder affecting bone formation, resulting in craniofacial malformations and bones that break easily. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SEC24D Gene-Disease associations (from GenCC):

• Cole-Carpenter syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• Cole-Carpenter syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24D	NM_014822.4	c.1041+1165C>T		intron_variant	Intron 8 of 22	ENST00000280551.11	NP_055637.2
SEC24D	NM_001318066.2	c.1044+1165C>T		intron_variant	Intron 8 of 22		NP_001304995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24D	ENST00000280551.11	c.1041+1165C>T		intron_variant	Intron 8 of 22	1	NM_014822.4	ENSP00000280551.6
SEC24D	ENST00000509818.5	n.*256+1165C>T		intron_variant	Intron 7 of 11	1		ENSP00000424085.1
SEC24D	ENST00000514561.5	n.*1015+1165C>T		intron_variant	Intron 9 of 22	1		ENSP00000422717.1
SEC24D	ENST00000419654.6	c.-292+1165C>T		intron_variant	Intron 8 of 19	5		ENSP00000388324.2

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10037 AN: 152098 Hom.: 381 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0661 AC: 10061 AN: 152216 Hom.: 384 Cov.: 32 AF XY: 0.0652 AC XY: 4852 AN XY: 74434

African (AFR) AF: 0.0972 AC: 4036 AN: 41518

American (AMR) AF: 0.0254 AC: 389 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.00788 AC: 38 AN: 4824

European-Finnish (FIN) AF: 0.100 AC: 1061 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4364 AN: 68012

Other (OTH) AF: 0.0497 AC: 105 AN: 2114

Alfa AF: 0.0611 Hom.: 133

Bravo AF: 0.0628

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.26
DANN	Benign	0.54
PhyloP100		-0.40
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: rs11098451; hg19: chr4-119717673;