chr4-56479493-G-A

Variant names:

• chr4-56479493-G-A
• rs4618376
• NM_006947.4:c.825+844G>A

Variant summary

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

The NM_006947.4(SRP72):​c.825+844G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 150,940 control chromosomes in the GnomAD database, including 3,304 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 0.20 (3304 hom., cov: 30)
• Consequence: SRP72 NM_006947.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 4 publications found

Genes affected

SRP72 (HGNC:11303): (signal recognition particle 72) This gene encodes the 72 kDa subunit of the signal recognition particle (SRP), a ribonucleoprotein complex that mediates the targeting of secretory proteins to the endoplasmic reticulum (ER). The SRP complex consists of a 7S RNA and 6 protein subunits: SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72, that are bound to the 7S RNA as monomers or heterodimers. SRP has at least 3 distinct functions that can be associated with the protein subunits: signal recognition, translational arrest, and ER membrane targeting by interaction with the docking protein. Mutations in this gene are associated with familial bone marrow failure. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

SRP72 Gene-Disease associations (from GenCC):

• autosomal dominant aplasia and myelodysplasia

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• acute myeloid leukemia

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

ENSG00000289393 (HGNC:58796):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006947.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP72	NM_006947.4	MANE Select	c.825+844G>A		intron	N/A	NP_008878.3
	SRP72	NM_001267722.2		c.642+2791G>A		intron	N/A	NP_001254651.1
	SRP72	NR_151856.2		n.844+844G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP72	ENST00000642900.1	MANE Select	c.825+844G>A		intron	N/A	ENSP00000495128.1
	SRP72	ENST00000510663.6	TSL:1	c.642+2791G>A		intron	N/A	ENSP00000424576.1
	SRP72	ENST00000505314.2	TSL:3	c.723+844G>A		intron	N/A	ENSP00000425190.3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29823 AN: 150840 Hom.: 3293 Cov.: 30

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.198 AC: 29835 AN: 150940 Hom.: 3304 Cov.: 30 AF XY: 0.204 AC XY: 15056 AN XY: 73712

African (AFR) AF: 0.136 AC: 5584 AN: 41186

American (AMR) AF: 0.351 AC: 5323 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3464

East Asian (EAS) AF: 0.194 AC: 996 AN: 5128

South Asian (SAS) AF: 0.224 AC: 1069 AN: 4780

European-Finnish (FIN) AF: 0.247 AC: 2515 AN: 10196

Middle Eastern (MID) AF: 0.208 AC: 60 AN: 288

European-Non Finnish (NFE) AF: 0.196 AC: 13255 AN: 67746

Other (OTH) AF: 0.229 AC: 477 AN: 2082

Alfa AF: 0.182 Hom.: 345

Bravo AF: 0.204

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.85
PhyloP100		-0.22
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: rs4618376; hg19: chr4-57345659;