rs4618376

Positions:

• chr4-56479493-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP72	NM_006947.4	c.825+844G>A		intron_variant		ENST00000642900.1	NP_008878.3
SRP72	NM_001267722.2	c.642+2791G>A		intron_variant			NP_001254651.1
SRP72	XM_024454192.2	c.825+844G>A		intron_variant			XP_024309960.1
SRP72	NR_151856.2	n.844+844G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1	c.825+844G>A		intron_variant			NM_006947.4	ENSP00000495128	P1
SRP72	ENST00000510663.6	c.642+2791G>A		intron_variant		1		ENSP00000424576
SRP72	ENST00000505314.2	c.725+844G>A		intron_variant		3		ENSP00000425190

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

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.229

Alfa AF: 0.183 Hom.: 336

Bravo AF: 0.204

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.85

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: rs4618376; hg19: chr4-57345659;