rs4834703

chr4-118770469-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014822.4(SEC24D):c.1042-2158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 152,242 control chromosomes in the GnomAD database, including 552 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 0.077 (552 hom., cov: 32)
• Consequence: SEC24D NM_014822.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC24D	NM_014822.4	c.1042-2158C>T		intron_variant		ENST00000280551.11
SEC24D	NM_001318066.2	c.1045-2158C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC24D	ENST00000280551.11	c.1042-2158C>T		intron_variant		1	NM_014822.4	P1
SEC24D	ENST00000509818.5	c.*257-2158C>T		intron_variant, NMD_transcript_variant		1
SEC24D	ENST00000514561.5	c.*1016-2158C>T		intron_variant, NMD_transcript_variant		1
SEC24D	ENST00000419654.6	c.-291-2158C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11729 AN: 152124 Hom.: 553 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.0770 AC: 11720 AN: 152242 Hom.: 552 Cov.: 32 AF XY: 0.0758 AC XY: 5647 AN XY: 74458

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.0854

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0438

Gnomad4 SAS AF: 0.0825

Gnomad4 FIN AF: 0.0690

Gnomad4 NFE AF: 0.0983

Gnomad4 OTH AF: 0.0900

Alfa AF: 0.0985 Hom.: 1208

Bravo AF: 0.0780

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	4.8
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs4834703; hg19: chr4-119691624;