rs4522565

Variant names:

• chr2-188333610-T-C
• rs4522565
• NM_016315.4:c.-172+41444T>C

Variant summary

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

The NM_016315.4(GULP1):​c.-172+41444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,026 control chromosomes in the GnomAD database, including 2,480 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 0.18 (2480 hom., cov: 31)
• Consequence: GULP1 NM_016315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 1 publications found

Genes affected

GULP1 (HGNC:18649): (GULP PTB domain containing engulfment adaptor 1) The protein encoded by this gene is an adapter protein necessary for the engulfment of apoptotic cells by phagocytes. Several transcript variants, some protein coding and some thought not to be protein coding, have been found for this gene. [provided by RefSeq, Nov 2011]

LINC01090 (HGNC:49201): (long intergenic non-protein coding RNA 1090)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GULP1	NM_016315.4	c.-172+41444T>C		intron_variant	Intron 1 of 11	ENST00000409830.6	NP_057399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GULP1	ENST00000409830.6	c.-172+41444T>C		intron_variant	Intron 1 of 11	1	NM_016315.4	ENSP00000386732.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27059 AN: 151906 Hom.: 2476 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.178 AC: 27097 AN: 152026 Hom.: 2480 Cov.: 31 AF XY: 0.180 AC XY: 13349 AN XY: 74318

African (AFR) AF: 0.183 AC: 7598 AN: 41444

American (AMR) AF: 0.154 AC: 2346 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1187 AN: 5150

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4816

European-Finnish (FIN) AF: 0.169 AC: 1785 AN: 10580

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11851 AN: 67974

Other (OTH) AF: 0.194 AC: 409 AN: 2112

Alfa AF: 0.173 Hom.: 288

Bravo AF: 0.175

Asia WGS AF: 0.242 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.82
PhyloP100		-0.94
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: rs4522565; hg19: chr2-189198337;