14-54782627-C-T

Position:

• chr14-54782627-C-T

Variant summary

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

The NM_015589.6(SAMD4A):​c.2045-1910C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,038 control chromosomes in the GnomAD database, including 23,392 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 0.55 (23392 hom., cov: 32)
• Consequence: SAMD4A NM_015589.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.07

Genes affected

SAMD4A (HGNC:23023): (sterile alpha motif domain containing 4A) Sterile alpha motifs (SAMs) in proteins such as SAMD4A are part of an RNA-binding domain that functions as a posttranscriptional regulator by binding to an RNA sequence motif known as the Smaug recognition element, which was named after the Drosophila Smaug protein (Baez and Boccaccio, 2005 [PubMed 16221671]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMD4A	NM_015589.6	c.2045-1910C>T		intron_variant		ENST00000554335.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD4A	ENST00000554335.6	c.2045-1910C>T		intron_variant		5	NM_015589.6	A1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83998 AN: 151920 Hom.: 23355 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.553 AC: 84096 AN: 152038 Hom.: 23392 Cov.: 32 AF XY: 0.549 AC XY: 40828 AN XY: 74314

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.532

Alfa AF: 0.530 Hom.: 3661

Bravo AF: 0.567

Asia WGS AF: 0.511 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.044
DANN	Benign	0.68

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: rs709939; hg19: chr14-55249345; COSMIC: COSV51878248; COSMIC: COSV51878248;