chr7-20784332-C-T

Variant names:

• chr7-20784332-C-T
• rs148247510
• NM_182700.6:c.1485G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_182700.6(SP8):​c.1485G>A​(p.Leu495Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,506,670 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (5 hom.)
• Consequence: SP8 NM_182700.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

Genes affected

SP8 (HGNC:19196): (Sp8 transcription factor) The protein encoded by this gene is an SP family transcription factor that in mouse has been shown to be essential for proper limb development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 7-20784332-C-T is Benign according to our data. Variant chr7-20784332-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BS2: High AC in GnomAd4 at 231 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182700.6. 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
	SP8	NM_182700.6	MANE Select	c.1485G>A	p.Leu495Leu	synonymous	Exon 2 of 2	NP_874359.2
	SP8	NM_198956.4		c.1431G>A	p.Leu477Leu	synonymous	Exon 3 of 3	NP_945194.1	Q8IXZ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP8	ENST00000418710.3	TSL:1 MANE Select	c.1485G>A	p.Leu495Leu	synonymous	Exon 2 of 2	ENSP00000408792.2	Q8IXZ3-4
	SP8	ENST00000361443.4	TSL:1	c.1431G>A	p.Leu477Leu	synonymous	Exon 3 of 3	ENSP00000354482.4	Q8IXZ3-3

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 231 AN: 151982 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00249

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00140 AC: 150 AN: 107482 AF XY: 0.00135

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.000860

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000355

Gnomad NFE exome AF: 0.00307

Gnomad OTH exome AF: 0.000308

GnomAD4 exome AF: 0.00279 AC: 3782 AN: 1354578 Hom.: 5 Cov.: 38 AF XY: 0.00265 AC XY: 1770 AN XY: 668326

African (AFR) AF: 0.000391 AC: 11 AN: 28166

American (AMR) AF: 0.00102 AC: 33 AN: 32488

Ashkenazi Jewish (ASJ) AF: 0.0000415 AC: 1 AN: 24096

East Asian (EAS) AF: 0.00 AC: 0 AN: 32816

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76078

European-Finnish (FIN) AF: 0.00107 AC: 36 AN: 33692

Middle Eastern (MID) AF: 0.000249 AC: 1 AN: 4022

European-Non Finnish (NFE) AF: 0.00335 AC: 3579 AN: 1066846

Other (OTH) AF: 0.00213 AC: 120 AN: 56374

GnomAD4 genome AF: 0.00152 AC: 231 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.00139 AC XY: 103 AN XY: 74336

African (AFR) AF: 0.000578 AC: 24 AN: 41508

American (AMR) AF: 0.00157 AC: 24 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00249 AC: 169 AN: 67996

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00214 Hom.: 0

Bravo AF: 0.00172

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SP8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.97
PhyloP100		1.0
Mutation Taster		=99/1	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: rs148247510; hg19: chr7-20823951;