rs562638

Variant names:

• chr19-39359149-A-G
• rs562638
• NM_001384574.2:c.196+2060A>G

Variant summary

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

The NM_001384574.2(SAMD4B):​c.196+2060A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,078 control chromosomes in the GnomAD database, including 11,743 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 0.28 (11743 hom., cov: 32)
• Consequence: SAMD4B NM_001384574.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 9 publications found

Genes affected

SAMD4B (HGNC:25492): (sterile alpha motif domain containing 4B) Enables RNA binding activity. Predicted to be involved in nuclear-transcribed mRNA poly(A) tail shortening. Predicted to act upstream of or within cerebellar neuron development. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384574.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD4B	NM_001384574.2	MANE Select	c.196+2060A>G		intron	N/A	NP_001371503.1	Q5PRF9
	SAMD4B	NM_001384565.1		c.196+2060A>G		intron	N/A	NP_001371494.1	Q5PRF9
	SAMD4B	NM_001384566.1		c.196+2060A>G		intron	N/A	NP_001371495.1	Q5PRF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD4B	ENST00000610417.5	TSL:2 MANE Select	c.196+2060A>G		intron	N/A	ENSP00000484229.1	Q5PRF9
	SAMD4B	ENST00000314471.10	TSL:1	c.196+2060A>G		intron	N/A	ENSP00000317224.5	Q5PRF9
	SAMD4B	ENST00000598913.5	TSL:1	c.196+2060A>G		intron	N/A	ENSP00000470237.1	M0QZ22

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42843 AN: 151960 Hom.: 11688 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0832

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.282 AC: 42952 AN: 152078 Hom.: 11743 Cov.: 32 AF XY: 0.276 AC XY: 20501 AN XY: 74342

African (AFR) AF: 0.721 AC: 29894 AN: 41442

American (AMR) AF: 0.156 AC: 2391 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3468

East Asian (EAS) AF: 0.0830 AC: 430 AN: 5178

South Asian (SAS) AF: 0.106 AC: 513 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1085 AN: 10586

Middle Eastern (MID) AF: 0.162 AC: 47 AN: 290

European-Non Finnish (NFE) AF: 0.107 AC: 7263 AN: 67982

Other (OTH) AF: 0.249 AC: 526 AN: 2110

Alfa AF: 0.278 Hom.: 7601

Bravo AF: 0.307

Asia WGS AF: 0.153 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.056
DANN	Benign	0.32
PhyloP100		-1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs562638;

hg19: chr19-39849789;