rs2255607

Variant names:

• chr10-68989028-G-A
• rs2255607
• NM_015634.4:c.196G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-68989028-G-A
• chr10-68989028-G-C
• chr10-68989028-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015634.4(KIFBP):​c.196G>A​(p.Gly66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,613,698 control chromosomes in the GnomAD database, including 172,227 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13505 hom., cov: 34)
  • Exomes 𝑓: 0.46 (158722 hom.)
• Consequence: KIFBP NM_015634.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.335
• Publications: 36 publications found

Genes affected

KIFBP (HGNC:23419): (kinesin family binding protein) This gene encodes a kinesin family member 1 binding protein that is characterized by two tetratrico peptide repeats. The encoded protein localizes to the mitochondria and may be involved in regulating transport of the mitochondria. Mutations in this gene are associated with Goldberg-Shprintzen megacolon syndrome. [provided by RefSeq, Mar 2010]

KIFBP Gene-Disease associations (from GenCC):

• Goldberg-Shprintzen syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6480684E-4).
• BP6: Variant 10-68989028-G-A is Benign according to our data. Variant chr10-68989028-G-A is described in ClinVar as Benign. ClinVar VariationId is 158696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015634.4. 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
	KIFBP	NM_015634.4	MANE Select	c.196G>A	p.Gly66Ser	missense	Exon 1 of 7	NP_056449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFBP	ENST00000361983.7	TSL:1 MANE Select	c.196G>A	p.Gly66Ser	missense	Exon 1 of 7	ENSP00000354848.4
	KIFBP	ENST00000638119.2	TSL:5	c.196G>A	p.Gly66Ser	missense	Exon 1 of 8	ENSP00000490026.1
	KIFBP	ENST00000674660.1		c.196G>A	p.Gly66Ser	missense	Exon 1 of 7	ENSP00000502562.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63049 AN: 152092 Hom.: 13502 Cov.: 34

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.404 AC: 100114 AN: 247738 AF XY: 0.406

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.372

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.484

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.461 AC: 673191 AN: 1461488 Hom.: 158722 Cov.: 65 AF XY: 0.456 AC XY: 331844 AN XY: 727048

African (AFR) AF: 0.346 AC: 11578 AN: 33472

American (AMR) AF: 0.301 AC: 13461 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 9133 AN: 26112

East Asian (EAS) AF: 0.355 AC: 14089 AN: 39690

South Asian (SAS) AF: 0.318 AC: 27445 AN: 86240

European-Finnish (FIN) AF: 0.403 AC: 21511 AN: 53312

Middle Eastern (MID) AF: 0.416 AC: 2398 AN: 5764

European-Non Finnish (NFE) AF: 0.492 AC: 547160 AN: 1111824

Other (OTH) AF: 0.438 AC: 26416 AN: 60376

GnomAD4 genome AF: 0.414 AC: 63053 AN: 152210 Hom.: 13505 Cov.: 34 AF XY: 0.407 AC XY: 30306 AN XY: 74396

African (AFR) AF: 0.347 AC: 14424 AN: 41558

American (AMR) AF: 0.350 AC: 5353 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1255 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1889 AN: 5158

South Asian (SAS) AF: 0.310 AC: 1499 AN: 4828

European-Finnish (FIN) AF: 0.394 AC: 4173 AN: 10592

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33017 AN: 67982

Other (OTH) AF: 0.430 AC: 910 AN: 2116

Alfa AF: 0.430 Hom.: 11281

Bravo AF: 0.411

TwinsUK AF: 0.491 AC: 1819

ALSPAC AF: 0.506 AC: 1952

ESP6500AA AF: 0.342 AC: 1507

ESP6500EA AF: 0.483 AC: 4153

ExAC AF: 0.410 AC: 49681

Asia WGS AF: 0.304 AC: 1058 AN: 3478

EpiCase AF: 0.476

EpiControl AF: 0.474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Goldberg-Shprintzen syndrome (4)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.2
DANN	Benign	0.84
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.00016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.34
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.011
Sift	Benign	0.55	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.043
MPC		0.45
ClinPred		0.00074	T
GERP RS		-0.11
PromoterAI		-0.071	Neutral
Varity_R		0.037
gMVP		0.12
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: rs2255607; hg19: chr10-70748784; COSMIC: COSV62555322; COSMIC: COSV62555322;