2-112177474-G-T

Variant names:

• chr2-112177474-G-T
• rs4849049
• NM_153214.3:c.532+1635G>T

Variant summary

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

The NM_153214.3(FBLN7):​c.532+1635G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,198 control chromosomes in the GnomAD database, including 1,641 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 0.14 (1641 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: FBLN7 NM_153214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• Publications: 2 publications found

Genes affected

FBLN7 (HGNC:26740): (fibulin 7) Predicted to enable calcium ion binding activity; heparan sulfate proteoglycan binding activity; and heparin binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within positive regulation of biomineralization. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153214.3. 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
	FBLN7	NM_153214.3	MANE Select	c.532+1635G>T		intron	N/A	NP_694946.2	Q53RD9-1
	FBLN7	NM_001128165.2		c.532+1635G>T		intron	N/A	NP_001121637.1	Q53RD9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN7	ENST00000331203.7	TSL:1 MANE Select	c.532+1635G>T		intron	N/A	ENSP00000331411.2	Q53RD9-1
	FBLN7	ENST00000409450.7	TSL:1	c.532+1635G>T		intron	N/A	ENSP00000387000.3	Q53RD9-2
	FBLN7	ENST00000409667.7	TSL:1	c.407-7727G>T		intron	N/A	ENSP00000386822.3	Q53RD9-4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20683 AN: 152056 Hom.: 1642 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0833 AC: 2 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 18

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.136 AC: 20691 AN: 152174 Hom.: 1641 Cov.: 32 AF XY: 0.135 AC XY: 10040 AN XY: 74382

African (AFR) AF: 0.0962 AC: 3991 AN: 41508

American (AMR) AF: 0.187 AC: 2866 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1753 AN: 5172

South Asian (SAS) AF: 0.101 AC: 488 AN: 4812

European-Finnish (FIN) AF: 0.0624 AC: 661 AN: 10598

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9920 AN: 68000

Other (OTH) AF: 0.140 AC: 294 AN: 2106

Alfa AF: 0.122 Hom.: 466

Bravo AF: 0.144

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.62
PhyloP100		0.35
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: rs4849049; hg19: chr2-112935051;