chr2-188594004-G-A

Variant names:

• chr2-188594004-G-A
• rs181641969
• NM_016315.4:c.908G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016315.4(GULP1):​c.908G>A​(p.Arg303Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,423,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R303T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GULP1 NM_016315.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11278802).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016315.4. 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
	GULP1	NM_016315.4	MANE Select	c.908G>A	p.Arg303Lys	missense	Exon 12 of 12	NP_057399.1	Q9UBP9-1
	GULP1	NM_001375948.1		c.1133G>A	p.Arg378Lys	missense	Exon 13 of 13	NP_001362877.1	H7BZV7
	GULP1	NM_001375949.1		c.1133G>A	p.Arg378Lys	missense	Exon 14 of 14	NP_001362878.1	H7BZV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GULP1	ENST00000409830.6	TSL:1 MANE Select	c.908G>A	p.Arg303Lys	missense	Exon 12 of 12	ENSP00000386732.1	Q9UBP9-1
	GULP1	ENST00000359135.7	TSL:1	c.908G>A	p.Arg303Lys	missense	Exon 12 of 12	ENSP00000352047.3	Q9UBP9-1
	GULP1	ENST00000451191.5	TSL:1	c.*5929G>A		3_prime_UTR	Exon 3 of 3	ENSP00000407131.1	H0Y6R1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1423148 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 710408

African (AFR) AF: 0.00 AC: 0 AN: 32736

American (AMR) AF: 0.00 AC: 0 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25680

East Asian (EAS) AF: 0.00 AC: 0 AN: 39370

South Asian (SAS) AF: 0.00 AC: 0 AN: 84980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078012

Other (OTH) AF: 0.00 AC: 0 AN: 59006

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.0072
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PhyloP100		5.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.12
Sift	Benign	0.068	T
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.30		Gain of methylation at R303 (P = 0.004)
MVP		0.40
MPC		0.18
ClinPred		0.62	D
GERP RS		1.3
Varity_R		0.075
gMVP		0.18
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs181641969; hg19: chr2-189458731;