chr16-47161828-A-T

Variant names:

• chr16-47161828-A-T
• rs1964810286
• NM_030790.5:c.1583T>A

Variant summary

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

The NM_030790.5(ITFG1):​c.1583T>A​(p.Ile528Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. I528T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ITFG1 NM_030790.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68
• Publications: 0 publications found

Genes affected

ITFG1 (HGNC:30697): (integrin alpha FG-GAP repeat containing 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ITFG1-AS1 (HGNC:51383): (ITFG1 antisense RNA 1)

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=0.11120573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITFG1	NM_030790.5	c.1583T>A	p.Ile528Lys	missense_variant	Exon 16 of 18	ENST00000320640.11	NP_110417.2
ITFG1	NM_001305002.2	c.1244T>A	p.Ile415Lys	missense_variant	Exon 16 of 18		NP_001291931.1
ITFG1-AS1	NR_110903.1	n.684+238A>T		intron_variant	Intron 4 of 4
ITFG1-AS1	NR_110904.1	n.519+238A>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITFG1	ENST00000320640.11	c.1583T>A	p.Ile528Lys	missense_variant	Exon 16 of 18	1	NM_030790.5	ENSP00000319918.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425976 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 711572

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32728

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39452

South Asian (SAS) AF: 0.00 AC: 0 AN: 85428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079594

Other (OTH) AF: 0.00 AC: 0 AN: 59128

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.0024	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.019	T;.;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.
PhyloP100		2.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.85	N;N;D
REVEL	Benign	0.21
Sift	Benign	0.94	T;T;D
Sift4G	Benign	0.95	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.43
MutPred		0.42		Gain of disorder (P = 0.0112);.;.;
MVP		0.29
MPC		0.75
ClinPred		0.88	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.76

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: rs1964810286; hg19: chr16-47195739;