2-188594004-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016315.4(GULP1):​c.908G>C​(p.Arg303Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000225 in 1,575,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: GULP1 NM_016315.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03696674).

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>C	p.Arg303Thr	missense	Exon 12 of 12	NP_057399.1	Q9UBP9-1
	GULP1	NM_001375948.1		c.1133G>C	p.Arg378Thr	missense	Exon 13 of 13	NP_001362877.1	H7BZV7
	GULP1	NM_001375949.1		c.1133G>C	p.Arg378Thr	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>C	p.Arg303Thr	missense	Exon 12 of 12	ENSP00000386732.1	Q9UBP9-1
	GULP1	ENST00000359135.7	TSL:1	c.908G>C	p.Arg303Thr	missense	Exon 12 of 12	ENSP00000352047.3	Q9UBP9-1
	GULP1	ENST00000451191.5	TSL:1	c.*5929G>C		3_prime_UTR	Exon 3 of 3	ENSP00000407131.1	H0Y6R1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 151988 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000220 AC: 55 AN: 250518 AF XY: 0.000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000874

Gnomad ASJ exome AF: 0.00130

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000228 AC: 324 AN: 1423140 Hom.: 0 Cov.: 24 AF XY: 0.000227 AC XY: 161 AN XY: 710404

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

American (AMR) AF: 0.0000674 AC: 3 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00101 AC: 26 AN: 25678

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

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

European-Finnish (FIN) AF: 0.000113 AC: 6 AN: 53190

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

European-Non Finnish (NFE) AF: 0.000253 AC: 273 AN: 1078006

Other (OTH) AF: 0.000271 AC: 16 AN: 59006

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41524

American (AMR) AF: 0.0000656 AC: 1 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 67930

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000270 Hom.: 0

Bravo AF: 0.000253

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000231 AC: 28

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.021	D
Polyphen		0.023	B
Vest4		0.54
MVP		0.32
MPC		0.41
ClinPred		0.081	T
GERP RS		1.3
Varity_R		0.093
gMVP		0.29
Mutation Taster		=66/34	polymorphism

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: rs181641969; hg19: chr2-189458731; COSMIC: COSV63066081; COSMIC: COSV63066081;