rs11098451

Positions:

• chr4-118796518-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.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

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=-0.97).
• 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/exons	MANE	Protein	UniProt
SEC24D	NM_014822.4	c.1041+1165C>T		intron_variant		ENST00000280551.11	NP_055637.2
SEC24D	NM_001318066.2	c.1044+1165C>T		intron_variant			NP_001304995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC24D	ENST00000280551.11	c.1041+1165C>T		intron_variant		1	NM_014822.4	ENSP00000280551	P1
SEC24D	ENST00000509818.5	c.*256+1165C>T		intron_variant, NMD_transcript_variant		1		ENSP00000424085
SEC24D	ENST00000514561.5	c.*1015+1165C>T		intron_variant, NMD_transcript_variant		1		ENSP00000422717
SEC24D	ENST00000419654.6	c.-292+1165C>T		intron_variant		5		ENSP00000388324

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

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00788

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0642

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0602 Hom.: 112

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

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: rs11098451; hg19: chr4-119717673;